Water → [1-(S)-(4-Fluorobenzyl)-2-(3-(S)-hydroxypyrrolidin-1-yl)-2-oxoethyl]carbamic acid tert-butyl ester

HRID 1693410ノート

反応式

HRID 1693410 の反応式
[C:1]([NH:8][C@H:9]([C:18]([OH:20])=O)[CH2:10][C:11]1[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[OH:21][C@H:22]1[CH2:26][CH2:25][NH:24][CH2:23]1.CCN(C(C)C)C(C)C.C1C=CC2N(O)N=NC=2C=1.O.CCN=C=NCCCN(C)C>CN(C=O)C>[C:4]([O:3][C:1](=[O:2])[NH:8][C@@H:9]([CH2:10][C:11]1[CH:12]=[CH:13][C:14]([F:17])=[CH:15][CH:16]=1)[C:18]([N:24]1[CH2:25][CH2:26][C@H:22]([OH:21])[CH2:23]1)=[O:20])([CH3:5])([CH3:6])[CH3:7]

参加物

8

反応物 6

HCID 962WaterHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 2733874(3S)-pyrrolidin-3-olHCID 7020910N-(tert-Butoxycarbonyl)-4-fluoro-L-phenylalanine

生成物 1

HCID 59753540[1-(S)-(4-Fluorobenzyl)-2-(3-(S)-hydroxypyrrolidin-1-yl)-2-oxoethyl]carbamic acid tert-butyl ester

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

To a stirred solution of (S)—N-Boc-4-fluorophenylalanine (5.08 g, 17.9 mmol) and (S)-3-hydroxypyrrolidine (1.05 mL, 19.7 mmol) in anhydrous DMF (200 mL), was added DIPEA (6.87 mL, 39.5 mmol) and HOBt.H2O (3.02 g, 19.7 mmol). The reaction mixture was stirred for 10 min at room temperature then EDCI (4.13 g, 21.5 mmol) was added and the resulting mixture stirred for 20 h at rt. The volatiles were removed in vacuo then the residue partitioned between water (200 mL) and ethyl acetate (200 mL). The layers were separated and the aqueous layer extracted with ethyl acetate (3×50 mL). The combined organics were washed with aqueous sodium hydroxide solution (2M, 3×50 mL), brine (100 mL), dried (MgSO4), filtered and concentrated in vacuo. The oily residue was purified via flash chromatography (SiO2, methanol/dichloromethane, 1:19, v/v) to give the title compound as a colourless oil which became a white solid on standing. m/z (ES+)=353 [M+H]+; RT=3.17 min.

後処理

  1. stirringthe resulting mixture stirred for 20 h at rt
  2. customThe volatiles were removed in vacuo
  3. customthe residue partitioned between water (200 mL) and ethyl acetate (200 mL)
  4. customThe layers were separated
  5. extractionthe aqueous layer extracted with ethyl acetate (3×50 mL)
  6. washThe combined organics were washed with aqueous sodium hydroxide solution (2M, 3×50 mL), brine (100 mL)
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe oily residue was purified via flash chromatography (SiO2, methanol/dichloromethane, 1:19, v/v)

出典と根拠

ORDレコード
ord-322d5846625f4ee8a137124397f92619
出典データセット
uspto-grants-2012_04
特許番号
US08158622B2

反応ノート

読み込み中…