Phenol → (2S)-2-[(1R,2S)-2-benzyloxycarbonyl-1-methylsulfanyl-propyl]-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 1582733Notes

Reaction equation

HRID 1582733 reaction equation
[C:1]([S:4]C)(C)=O.O(CC)[K].C1(O)C=CC=CC=1.[C:17]([O:21][C:22]([N:24]1[CH2:28][CH2:27][CH2:26][C@H:25]1[CH:29]=[C:30]([C:32]([O:34][CH2:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)=[O:33])[CH3:31])=[O:23])([CH3:20])([CH3:19])[CH3:18]>C1COCC1>[C:17]([O:21][C:22]([N:24]1[CH2:28][CH2:27][CH2:26][C@H:25]1[C@H:29]([S:4][CH3:1])[C@H:30]([C:32]([O:34][CH2:35][C:36]1[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=1)=[O:33])[CH3:31])=[O:23])([CH3:18])([CH3:19])[CH3:20]

Participants

6

Reactant 4

HCID 996PhenolHCID 73750S-Methyl thioacetateHCID 69343930(S)-2-(2-Benzyloxycarbonyl-propenyl)-pyrrolidine-1-carboxylic acid tert-butyl esterHCID 178473702HCID 178473702, compound

Product 1

HCID 58660116(2S)-2-[(1R,2S)-2-benzyloxycarbonyl-1-methylsulfanyl-propyl]-pyrrolidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirred solution of AcSMe (24.4 g, 0.27 mol) in THF (580 ml) cooled in an ice-bath was added KOEt (22.8 g, 0.27 mol). After stirring for 3.5 h at room temperature, phenol (11.9 ml, 0.14 mol) and a solution of (2S)-2-(2-benzyloxycarbonyl-propenyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (15.6 g, 0.045 mol) in THF (50 ml) were successively added to the mixture. After 45 min, the mixture was quenched with saturated NH4Cl aqueous solution and concentrated in vacuo. The residue was diluted with EtOAc (600 ml), and washed with 1N NaOH aqueous solution (300 ml×3) and saturated brine (200 ml). The organic layer was dried over anhydrous Na2SO4 and then concentrated in vacuo. The residue was purified by column chromatography on silica gel (hexane/EtOAc=9/1) to give (2S)-2-[(1R,2S)-2-benzyloxycarbonyl-1-methylsulfanyl-propyl]-pyrrolidine-1-carboxylic acid tert-butyl ester which was contaminated with PhOH. The collected fraction which included (2S)-2-[(1R,2S)-2-benzyloxycarbonyl-1-methylsulfanyl-propyl]-pyrrolidine-1-carboxylic acid tert-butyl ester was washed with 5N NaOH aqueous solution (300 ml) and H2O (300 ml) to remove phenol, and dried over anhydrous MgSO4. The organic layer was concentrated in vacuo to obtain (2S)-2-[(1R,2S)-2-benzyloxycarbonyl-1-methylsulfanyl-propyl]-pyrrolidine-1-carboxylic acid tert-butyl ester (12.5 g, 70%).

Workup

  1. waitAfter 45 min
  2. customthe mixture was quenched with saturated NH4Cl aqueous solution
  3. concentrationconcentrated in vacuo
  4. additionThe residue was diluted with EtOAc (600 ml)
  5. washwashed with 1N NaOH aqueous solution (300 ml×3) and saturated brine (200 ml)
  6. dry with materialThe organic layer was dried over anhydrous Na2SO4
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by column chromatography on silica gel (hexane/EtOAc=9/1)

Sources & evidence

ORD record
ord-d3b0c828cc4a4ae18bdc097b286156f8
Source dataset
uspto-grants-2004_05
Patent number
US06737409B2

Reaction notes

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