Sodium Hydroxide → (S)-1-((Benzyloxy)carbonyl)-4,4-difluoropyrrolidine-2-carboxylic acid

HRID 1733347Notes

Reaction equation

HRID 1733347 reaction equation
[C:1]([N:11]1[CH2:19][C:18]([F:21])([F:20])[CH2:17][C@H:12]1[C:13]([O:15]C)=[O:14])([O:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:2].[OH-].[Na+]>CO>[C:1]([N:11]1[CH2:19][C:18]([F:20])([F:21])[CH2:17][C@H:12]1[C:13]([OH:15])=[O:14])([O:3][CH2:4][C:5]1[CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=1)=[O:2]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 497579381-benzyl 2-methyl (2S)-4,4-difluoropyrrolidine-1,2-dicarboxylate

Product 1

HCID 53909714(S)-1-((Benzyloxy)carbonyl)-4,4-difluoropyrrolidine-2-carboxylic acid

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of 5.6 grams of N-carbobenzyloxy-4,4-difluoro-L-proline, methyl ester in 50 ml. of methanol is treated dropwise with 11.5 ml. of 2 N sodium hydroxide solution at 0°-5°. The reaction mixture is left at 0° for 1 hour and is then allowed to warm to room temperature overnight. The reaction mixture is concentrated under reduced pressure to about one-half its original volume and is then diluted with 100 ml. of water. The aqueous reaction mixture is extracted with ether and the ether extracts discarded. The aqueous solution is acidified with cooling with dilute hydrochloric acid to pH 2 and is then extracted with ethyl acetate (3×50 ml.). The ethyl acetate extracts are combined and washed with saturated sodium chloride solution, dried over anhydrous magnesium sulfate and concentrated to yield the desired product, N-carbobenzyloxy-4,4-difluoro-L-proline. It is purified by conversion to the cyclohexylamine salt, m.p. 180°-185° [α]D26 -24° (c=1%; ethanol).

Workup

  1. customat 0°-5°
  2. concentrationThe reaction mixture is concentrated under reduced pressure to about one-half its original volume
  3. additionis then diluted with 100 ml
  4. extractionThe aqueous reaction mixture is extracted with ether
  5. temperaturewith cooling with dilute hydrochloric acid to pH 2
  6. extractionis then extracted with ethyl acetate (3×50 ml.)
  7. washwashed with saturated sodium chloride solution
  8. dry with materialdried over anhydrous magnesium sulfate
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-d505146449b743f68306c0133ba3cb0e
Source dataset
uspto-grants-1980_12
Patent number
US04241076

Reaction notes

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