Diisopropylethylamine → (R)-2-(2-ethoxy-5-oxo-tetrahydrofuran-3-ylcarbamoyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 2215957Notes

Reaction equation

HRID 2215957 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C@H:9]1[C:13]([OH:15])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(C(C)C)CC)(C)C.F[P-](F)(F)(F)(F)F.CN(C)C(F)=[N+](C)C.C1(P(=[N:59][CH:60]2[CH:64]([O:65][CH2:66][CH3:67])[O:63][C:62](=[O:68])[CH2:61]2)(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>ClCCl.C(OCC)(=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C@@H:9]1[C:13](=[O:15])[NH:59][CH:60]1[CH2:61][C:62](=[O:68])[O:63][CH:64]1[O:65][CH2:66][CH3:67])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 850831,2-Pyrrolidinedicarboxylic acid, 1-(1,1-dimethylethyl) ester, (2S)-HCID 2774761Tetramethylfluoroformamidinium hexafluorophosphateHCID 865885854-[(Triphenylphosphoranylidene)amino]-5-ethoxy-dihydrofuran-2-one

Product 1

HCID 68578131(R)-2-(2-ethoxy-5-oxo-tetrahydrofuran-3-ylcarbamoyl)-pyrrolidine-1-carboxylic acid tert-butyl esterYield 65%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

A solution of (S)-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester (0.11 g, 0.5 mmol), di-isopropylethylamine (0.18 mL, 1.0 mmol), and tetramethylfluoroformamidinium hexafluorophosphate (TFFH) (0.13 g, 0.5 mmol) in dichloromethane (3 mL) was stirred at room temperature under nitrogen for 3 h. A solution of 4-[(triphenylphosphoranylidene)amino]-5-ethoxy-dihydrofuran -2-one (0.20 g, 0.5 mmol) in dichloromethane (3 mL) was added and the mixture was stirred for 24 h. The reaction was diluted with ethyl acetate, was washed with 10% sodium bisulfate, saturated sodium bicarbonate, and brine, was dried over sodium sulfate, and was evaporated. Purification by flash chromatography (SiO2) eluted with 1:1 ethyl acetate:hexanes provided (R)-2-(2-ethoxy-5-oxo-tetrahydrofuran -3-ylcarbamoyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (0.11 g, 65% yield) as a very viscous, pale yellow oil.

Workup

  1. washwas washed with 10% sodium bisulfate, saturated sodium bicarbonate, and brine
  2. dry with materialwas dried over sodium sulfate
  3. customwas evaporated
  4. customPurification by flash chromatography (SiO2)
  5. washeluted with 1:1 ethyl acetate

Sources & evidence

ORD record
ord-80f7fba0247c4d4f8740d6afae8356c8
Source dataset
uspto-grants-2006_09
Patent number
US07109357B2

Reaction notes

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