Acrylonitrile → 3,4-dihydro-2H-1-benzopyran-2-carboxylic acid

HRID 1603679

반응식

HRID 1603679 반응식
NC1CCC=CO1.C(#N)C=C.N12CCN(CC1)CC2.C(C1C=CC2C=CC=CC=2O1)#N.[O:32]1[C:37]2[CH:38]=[CH:39][CH:40]=[CH:41][C:36]=2[CH:35]=[CH:34][CH:33]1[C:42]([OH:44])=[O:43].[OH-].[Na+]>C(O)C.[Pd]>[O:32]1[C:37]2[C:36](=[CH:41][CH:40]=[CH:39][CH:38]=2)[CH2:35][CH2:34][CH:33]1[C:42]([OH:44])=[O:43]

참가 물질

9

반응물 6

HCID 7855AcrylonitrileHCID 9237DabcoHCID 14798Sodium HydroxideHCID 15552178CyanobenzopyranHCID 21879658Benzopyran carboxylic acid2회HCID 67079662Dihydroaminopyran

생성물 1

HCID 27236653,4-dihydro-2H-1-benzopyran-2-carboxylic acid

시약·촉매·용매 2

HCID 23938Palladium촉매HCID 702Ethanol용매

실험 절차

An alternative route to the dihydroaminopyran, O, again starting with Aldehyde M, is described in Thorberg et al., supra. Aldehyde M is reacted with acrylonitrile and 1,4-diazabicyclo[2.2.2]octane (DABCO) at reflux. The cyanobenzopyran is converted to the corresponding benzopyran carboxylic acid with aqueous sodium hydroxide. The benzopyran carboxylic acid (Q) is esterified using a mineral acid in ethanol and reduced by hydrogenation over 5% Pd/C to provide a chroman carboxylic acid. The chroman carboxylic acid is reacted with diphenylphosphorazidate and trimethylamine in benzene at reflux followed by addition of benzyl alcohol and an additional 24 hours at reflux. This provides a benzyloxycarbonyl (SOC) protected amine (R). Hydrogenation of the BOC protected amine provided racemic aminochroman (Q) (Step v). The racemic amine (Q) was resolved using the technique described in WO 93/07135 (Step vi). The resolved (R)-amine (P) is converted to a compound having formula VII following the procedures described in WO 95/11891 (Step vii).

후처리

  1. temperatureat reflux

출처 및 근거

ORD 기록
ord-98c72d6630444c11935e0552629283fc
출처 데이터셋
uspto-grants-1999_11
특허 번호
US05990114

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