合成路线:The cyclization of 4-hydroxyacetophenone (I) with 3-chloro-3-methyl-1-butyne (II) gives 6-acetyl-2,2-dimethyl-2H-1-benzopyran (III),which is enantioselectively epoxidized by means of Mn+3 salen catalysts,yielding the chiral epoxide (IV).The cleavage of the epoxide ring of (IV) with ammonia in ethanol affords the (3R,4S)-trans-aminoalcohol (V).The acylation of (V) with 3-chloro-4-fluorobenzoyl chloride (VI) and triethylamine yields the (3R,4S)-trans-amide (VII).The cyclization of (VII) by means of diethylaminosulfur trifluoride (DAST) in dichloromethane affords the (3aS-cis)-oxazoline (VIII),which is finally treated with 5N H2SO4.
参考文献标题:Benzopyrans and their use as therapeutic agents
文献作者:Chan,W.N.; Morgan,H.K.A.; Thompson,M.; Evans,J.M.(SmithKline Beecham plc)
参考来源:EP 0764157; JP 1998501251; US 5760074; WO 9534545
合成路线:The cyclization of 4-hydroxyacetophenone (I) with 3-chloro-3-methyl-1-butyne (II) gives 6-acetyl-2,2-dimethyl-2H-1-benzopyran (III),which is enantioselectively epoxidized by means of Mn+3 salen catalysts,yielding the chiral epoxide (IV).The cleavage of the epoxide ring of (IV) with ammonia in ethanol affords the (3R,4S)-trans-aminoalcohol (V).The acylation of (V) with 3-chloro-4-fluorobenzoyl chloride (VI) and triethylamine yields the (3R,4S)-trans-amide (VII).The cyclization of (VII) by means of diethylaminosulfur trifluoride (DAST) in dichloromethane affords the (3aS-cis)-oxazoline (VIII),which is finally treated with 5N H2SO4.
参考文献标题:Chiral catalysts and epoxidation reactions catalyzed thereby
文献作者:Attrill,R.P.; Bell,D.; Miller,D.(SmithKline Beecham plc)
参考来源:WO 9403271
合成路线:The cyclization of 4-hydroxyacetophenone (I) with 3-chloro-3-methyl-1-butyne (II) gives 6-acetyl-2,2-dimethyl-2H-1-benzopyran (III),which is enantioselectively epoxidized by means of Mn+3 salen catalysts,yielding the chiral epoxide (IV).The cleavage of the epoxide ring of (IV) with ammonia in ethanol affords the (3R,4S)-trans-aminoalcohol (V).The acylation of (V) with 3-chloro-4-fluorobenzoyl chloride (VI) and triethylamine yields the (3R,4S)-trans-amide (VII).The cyclization of (VII) by means of diethylaminosulfur trifluoride (DAST) in dichloromethane affords the (3aS-cis)-oxazoline (VIII),which is finally treated with 5N H2SO4.
合成路线:The cyclization of 4-hydroxyacetophenone (I) with 3-chloro-3-methyl-1-butyne (II) gives 5-acetyl-2,2-dimethyl-2H-1-benzopyran (III),which is enantioselectively epoxidized catalyzed by chiral salen Mn(III) catalysts to yield the (3R,4R)-epoxide (IV).The reaction of (IV) with ammonia in ethanol affords the (3R,4S)-aminoalcohol (V),which is finally acylated with 4-fluorobenzoyl chloride (VI) and TEA in dichloromethane to provide the target amide.Alternatively,the target amide can also be obtained by direct cleavage of the epoxide ring of (IV) with 4-fluorobenzamide (VII) by means of tBu-OK in tert-butanol.
参考文献标题:Synthesis of novel trans-4-(substituted-benzamido)-3,4-dihydro-2H-benzo[b]-pyran-3-ol derivatives as potential anticonvulsant agents with a distinctive binding profile
文献作者:Chan,W.N.; Evans,J.M.; Hadley,M.S.; Herdon,H.J.; Jerman,J.C.; Morgan,H.K.; Stean,T.O.; Thompson,M.; Upton,N.; Vong,A.K.
参考来源:J Med Chem 1996,39(23),4537
合成路线:The cyclization of 4-hydroxyacetophenone (I) with 3-chloro-3-methyl-1-butyne (II) gives 6-acetyl-2,2-dimethyl-2H-1-benzopyran (III),which is enantioselectively epoxidized by means of Mn+3 salen catalysts,yielding the chiral epoxide (IV).The cleavage of the epoxide ring of (IV) with ammonia in ethanol affords the (3R,4S)-trans-aminoalcohol (V).The acylation of (V) with 3-chloro-4-fluorobenzoyl chloride (VI) and triethylamine yields the (3R,4S)-trans-amide (VII).The cyclization of (VII) by means of diethylaminosulfur trifluoride (DAST) in dichloromethane affords the (3aS-cis)-oxazoline (VIII),which is finally treated with 5N H2SO4.
参考文献标题:Tonabersat
文献作者:Castar,J.; Leeson,P.; Rabasseda,X.
参考来源:Drugs Fut 1999,24(10),1078
产品链接: CAS No. 175013-84-0››