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

HRID 751108

反応式

HRID 751108 の反応式
[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]

参加物

8

反応物 4

HCID 176Acetic Acid2 回HCID 5049666Sodium triacetoxyborohydride2 回HCID 16732142tert-Butyl-(2S,3R)-3-{[tert-butyl(dimethyl)silyl]oxy}-2-formylpyrrolidine-1-carboxylateHCID 218754134-Amino-2-chloro-3-methylbenzonitrile

生成物 1

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

試薬・触媒・溶媒 3

HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒HCID 8857Ethyl Acetate溶媒

実験手順

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]+.

後処理

  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)

出典と根拠

ORDレコード
ord-6acbfa4145994ae2adadcb061539d10a
出典データセット
uspto-grants-2008_07
特許番号
US07405234B2

関連ノート

読み込み中…