Hydrochloric Acid → 2-Ethoxy-3-(2,2,2-trifluoro-acetylamino)-pyrrolidine-1-carboxylic acid benzyl ester

HRID 1976548Notes

Reaction equation

HRID 1976548 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:15][CH2:14][CH:13]([NH:16][C:17](=[O:22])[C:18]([F:21])([F:20])[F:19])[C:12]1=[O:23])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[BH4-].[Na+].Cl.S(=O)(=O)(O)O.C(=O)(O)[O-].[Na+].[CH2:37](O)[CH3:38]>O1CCOCC1>[CH2:1]([O:8][C:9]([N:11]1[CH2:15][CH2:14][CH:13]([NH:16][C:17](=[O:22])[C:18]([F:21])([F:19])[F:20])[CH:12]1[O:23][CH2:37][CH3:38])=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

8

Reactant 6

HCID 313Hydrochloric Acid2×HCID 702EthanolHCID 1118Sulfuric AcidHCID 516892Sodium BicarbonateHCID 4311764Sodium borohydride2×HCID 107114652-Oxo-3-(2,2,2-trifluoro-acetylamino)-pyrrolidine-1-carboxylic acid benzyl ester

Product 1

HCID 541161922-Ethoxy-3-(2,2,2-trifluoro-acetylamino)-pyrrolidine-1-carboxylic acid benzyl ester

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Procedure

To Intermediate 4 (34 g) in ethanol (1070 ml) at −5° C. was added sodium borohydride (9.86 g). A solution of 4M hydrogen chloride in 1,4-dioxan (20 ml) was then added dropwise. Periodically further portions of 4M hydrogen chloride in 1,4-dioxan (2×5 ml, 1×10 ml) and sodium borohydride (2 g) were added. After 3 h, concentrated sulphuric acid (11 ml) was added and the mixture warmed to room temperature for 2 h. Saturated aqueous sodium bicarbonate (300 ml) was then added and the ethanol and dioxan removed in vacuo. The residue was diluted with water (500 ml) and extracted with ethyl acetate (3×500 ml). The combined extracts were washed with brine and dried (MgSO4). The solvent was removed in vacuo and the residue purified by flash chromatography on silica gel 9385 eluting with ether, to give the title compound (21 g). Mass spec. MNH4+ (found) 378 MNH4+ (calculated) 378

Workup

  1. customthe ethanol and dioxan removed in vacuo
  2. additionThe residue was diluted with water (500 ml)
  3. extractionextracted with ethyl acetate (3×500 ml)
  4. washThe combined extracts were washed with brine
  5. dry with materialdried (MgSO4)
  6. customThe solvent was removed in vacuo
  7. customthe residue purified by flash chromatography on silica gel 9385 eluting with ether

Sources & evidence

ORD record
ord-e6574531a0d24c5a8f58e16e3fbf49e0
Source dataset
uspto-grants-2001_05
Patent number
US06228853B1

Reaction notes

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