Acetic Acid → (2R,3R)-N-tert-Butyloxycarbonyl-3-(tert-butyldimethylsiloxy)-2-[(3-chloro-4-cyano-2-methylphenylamino)methyl]pyrrolidine

HRID 501592

반응식

HRID 501592 반응식
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@@H:10]([O:13][Si:14]([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15])[C@H:9]1[CH:21]=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH2:23][C:24]1[CH:31]=[CH:30][C:27]([C:28]#[N:29])=[C:26]([Cl:32])[C:25]=1[CH3:33].[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].CC(O)=O>CN(C=O)C.C(Cl)Cl.CCOC(C)=O>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@@H:10]([O:13][Si:14]([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15])[C@H:9]1[CH2:21][NH:23][C:24]1[CH:31]=[CH:30][C:27]([C:28]#[N:29])=[C:26]([Cl:32])[C:25]=1[CH3:33])=[O:7])([CH3:2])([CH3:3])[CH3:4]

참가 물질

8

반응물 4

HCID 176Acetic Acid2회HCID 5049666Sodium triacetoxyborohydride2회HCID 16732142tert-Butyl-(2S,3R)-3-{[tert-butyl(dimethyl)silyl]oxy}-2-formylpyrrolidine-1-carboxylateHCID 218754134-Amino-2-chloro-3-methylbenzonitrile

생성물 1

HCID 59424841(2R,3R)-N-tert-Butyloxycarbonyl-3-(tert-butyldimethylsiloxy)-2-[(3-chloro-4-cyano-2-methylphenylamino)methyl]pyrrolidine수율 63%

시약·촉매·용매 3

HCID 6228Dimethylformamide용매HCID 6344Dichloromethane용매HCID 8857Ethyl Acetate용매

실험 절차

To a solution of (2S,3R)-3-(tert-Butyldimethylsilanyloxy)-2-formyl-pyrrolidine-1-carboxylic acid tert-butyl ester (51C) (661 mg, 2.0 mmol) in 5% DMF in CH2Cl2 (10 mL) at rt was added 4-amino-2-chloro-3-methyl-benzonitrile (340 mg, 2.04 mmol) followed by NaBH(OAc)3 (636 mg, 3.0 mmol) and HOAc (180 μL, 3 mmol). The reaction was stirred under nitrogen at rt for 18 h. Additional portions of NaBH(OAc)3 (424 mg, 2.0 mmol) and HOAc (120 μL, 2 mmol) were added, and the reaction was stirred for an additional 18 h. The reaction was diluted with EtOAc (50 mL) and the organic layer was washed with saturated aqueous NaHCO3 (50 ml), dried (MgSO4), filtered and concentrated. Purification via flash chromatography (silica gel, 0 to 15% EtOAc/hexanes) provided the title compound (605 mg, 1.26 mmol, 63%). MS m/z 480 [M+H]+.

후처리

  1. stirringthe reaction was stirred for an additional 18 h
  2. washthe organic layer was washed with saturated aqueous NaHCO3 (50 ml)
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification via flash chromatography (silica gel, 0 to 15% EtOAc/hexanes)

출처 및 근거

ORD 기록
ord-182c28df328b40b69754c4df7d5a5fb1
출처 데이터셋
uspto-grants-2010_08
특허 번호
US07772267B2

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