Hydrochloric Acid → (2S,4S)-1-(Tert-butoxycarbonyl)-4-(2,4-difluoro-phenoxy)-2-pyrrolidinecarboxylic acid

HRID 354403Notes

Reaction equation

HRID 354403 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH:11]([O:13][C:14]2[CH:19]=[CH:18][C:17]([F:20])=[CH:16][C:15]=2[F:21])[CH2:10][CH:9]1[C:22]([O:24]C)=[O:23])=[O:7])([CH3:4])([CH3:3])[CH3:2].[OH-].[Na+].Cl>C1COCC1>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH:11]([O:13][C:14]2[CH:19]=[CH:18][C:17]([F:20])=[CH:16][C:15]=2[F:21])[CH2:10][CH:9]1[C:22]([OH:24])=[O:23])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 69333072HCID 69333072, compound

Product 1

HCID 23511756(2S,4S)-1-(Tert-butoxycarbonyl)-4-(2,4-difluoro-phenoxy)-2-pyrrolidinecarboxylic acidYield 46%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of methyl 1-(tert-butoxycarbonyl)-4-(2,4-difluorophenoxy)pyrrolidine-2-carboxylate (5.82 g, 16.3 mmol) in THF (130 ml) was added 0.25 N NaOH (130 ml, 32.6 mmol). The resulting mixture was stirred overnight. The mixture was poured into 1 N HCl (100 ml) and extracted with CHCl3 (2×200 ml). The extracts were dried over MgSO4 and evaporated. The residue was chromatographed on silica gel with CHCl3-EtOAc (4:1) as eluent to give 1-(tert-butoxycarbonyl)-4-(2,4-difluorophenoxy)pyrrolidine-2-carboxylic acid (2.55 g, 46%) as a colorless foam. 1H-NMR (CDCl3) δ1.42-1.47 (m, 9 H), 2.29-2.74 (series of m, 2 H), 3.66-3.71 (m, 2 H), 4.46-4.51 (m, 1 H), 4.83 (m, 1 H), 6.73-6.95 (m, 3 H).

Workup

  1. extractionextracted with CHCl3 (2×200 ml)
  2. dry with materialThe extracts were dried over MgSO4
  3. customevaporated
  4. customThe residue was chromatographed on silica gel with CHCl3-EtOAc (4:1) as eluent

Sources & evidence

ORD record
ord-87ea407672cb43a1abb9f02b4774156d
Source dataset
uspto-grants-2004_06
Patent number
US06756378B2

Reaction notes

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