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

HRID 751665Notes

Reaction equation

HRID 751665 reaction equation
[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]

Participants

8

Reactant 6

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-2dd6b0f4da5f4fcd88bfc6c64e923e39
Source dataset
uspto-grants-2008_07
Patent number
US07405210B2

Reaction notes

Loading…