Benzoic Acid → (2S,3R)-N-tert-Butoxycarbonyl-3-benzoyloxy-2-pyrrolidinecarboxylic acid methyl ester

HRID 1612066Notes

Reaction equation

HRID 1612066 reaction equation
[CH3:1][O:2][C:3]([C@@H:5]1[C@@H:9]([OH:10])[CH2:8][CH2:7][N:6]1[C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])=[O:4].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:37](O)(=[O:44])[C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1.CCOC(/N=N/C(OCC)=O)=O>C1COCC1>[CH3:1][O:2][C:3]([C@@H:5]1[C@H:9]([O:10][C:37](=[O:44])[C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)[CH2:8][CH2:7][N:6]1[C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])=[O:4]

Participants

6

Reactant 4

HCID 243Benzoic AcidHCID 11776TriphenylphosphineHCID 5462977Diethyl azodicarboxylateHCID 147292531-tert-butyl 2-methyl (2S,3S)-3-hydroxypyrrolidine-1,2-dicarboxylate

Product 1

HCID 58583618(2S,3R)-N-tert-Butoxycarbonyl-3-benzoyloxy-2-pyrrolidinecarboxylic acid methyl esterYield 94.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 7A (13.5 g, 55 mmol) in anhydrous THF (500 mL) was added triphenylphosphine (26 g, 99 mmol), followed by benzoic acid (10.1 g, 82.7 mmol) and DEAD (9.5 mL, 60 mmol). The reaction mixture was stirred at RT for 2 hours, then partitioned between water and CH2Cl2. The organic phase was washed with saturated aqueous NaHCO3 and brine, dried over Na2SO4 and filtered. The filtrate was concentrated under reduced pressure to give a crude product, which was chromatographed (silica gel) eluting with 15% EtOAc/hexane to give 18.1 g of the title compound as a colorless oil.

Workup

  1. custompartitioned between water and CH2Cl2
  2. washThe organic phase was washed with saturated aqueous NaHCO3 and brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. customto give a crude product, which
  7. customwas chromatographed (silica gel)
  8. washeluting with 15% EtOAc/hexane

Sources & evidence

ORD record
ord-99751f22977448b480473c35f6240a4b
Source dataset
uspto-grants-2006_01
Patent number
US06992102B2

Reaction notes

Loading…