Sodium Hydroxide → 1-[1-Benzyloxycarbonyl-4-(S)-fluoro-3-(S)-pyrrolidinyl]-cyclopropanecarboxylic acid

HRID 635106Notes

Reaction equation

HRID 635106 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:15][C@H:14]([C:16]2([C:19]([O:21]CC)=[O:20])[CH2:18][CH2:17]2)[C@H:13]([F:24])[CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-].[Na+]>C(O)C>[CH2:1]([O:8][C:9]([N:11]1[CH2:12][C@@H:13]([F:24])[C@@H:14]([C:16]2([C:19]([OH:21])=[O:20])[CH2:18][CH2:17]2)[CH2:15]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 110350361-Benzyloxycarbonyl-4-(S)-(1-ethoxycarbonylcyclopropyl)-3-(S)-fluoropyrrolidine

Product 1

HCID 109797271-[1-Benzyloxycarbonyl-4-(S)-fluoro-3-(S)-pyrrolidinyl]-cyclopropanecarboxylic acidYield 92.1%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
40 °C

Procedure

1-Benzyloxycarbonyl-4-(S)-(1-ethoxycarbonylcyclopropyl)-3-(S)-fluoropyrrolidine (4.67 g, 13.92 mmol) was dissolved in ethanol (50 ml). Then a 1 N aqueous solution of sodium hydroxide (50 ml) was added dropwise into this solution. Then the liquid reaction mixture was stirred at 40° C. for 1.5 hours and ethanol was removed by evaporation under reduced pressure. Water (50 ml) was added to the residue followed by washing with chloroform (100 ml). The aqueous layer was separated and acidified by adding dropwise 1 N hydrochloric acid thereinto. Next, it was extracted successively with chloroform (200 ml×2) and diethyl ether (100 ml). The combined organic layer was dried over anhydrous sodium sulfate. After filtering, the filtrate was concentrated under reduced pressure to obtain 3.94 g (92.1%) of the title compound as a colorless amorphous substance.

Workup

  1. customThen the liquid reaction mixture
  2. customethanol was removed by evaporation under reduced pressure
  3. additionWater (50 ml) was added to the residue
  4. washby washing with chloroform (100 ml)
  5. customThe aqueous layer was separated
  6. additionby adding dropwise 1 N hydrochloric acid
  7. extractionNext, it was extracted successively with chloroform (200 ml×2) and diethyl ether (100 ml)
  8. dry with materialThe combined organic layer was dried over anhydrous sodium sulfate
  9. filtrationAfter filtering
  10. concentrationthe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-2d3e4e38e191486f9072865c01225d4e
Source dataset
uspto-grants-2001_02
Patent number
US06184388B2

Reaction notes

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