Sodium ethoxide → ((3S*,4R*)-1-Benzyl-4-hydroxymethyl-pyrrolidin-3-ylmethyl)-isopropyl-carbamic acid tert-butyl ester

HRID 1158481Notes

Reaction equation

HRID 1158481 reaction equation
C(OC(=O)[O:7][CH2:8][C@@H:9]1[C@H:13]([CH2:14][N:15]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH:16]([CH3:18])[CH3:17])[CH2:12][N:11]([CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH2:10]1)(C)(C)C.CC[O-].[Na+]>CCO>[C:22]([O:21][C:19](=[O:20])[N:15]([CH2:14][C@H:13]1[C@@H:9]([CH2:8][OH:7])[CH2:10][N:11]([CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH2:12]1)[CH:16]([CH3:17])[CH3:18])([CH3:24])([CH3:25])[CH3:23]

Participants

4

Reactant 2

HCID 2723922Sodium ethoxideHCID 86622401Carbonic acid (3R*,4S*)-1-benzyl-4-[(tert-butoxycarbonyl-isopropyl-amino)-methyl]-pyrrolidin-3-ylmethyl ester tert-butyl ester

Product 1

HCID 68616191((3S*,4R*)-1-Benzyl-4-hydroxymethyl-pyrrolidin-3-ylmethyl)-isopropyl-carbamic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of carbonic acid (3R*,4S*)-1-benzyl-4-[(tert-butoxycarbonyl-isopropyl-amino)-methyl]-pyrrolidin-3-ylmethyl ester tert-butyl ester (2.02 g, 4.31 mmol) and NaOEt (0.59 g, 8.62 mmol) in EtOH (35 mL) is stirred for 2 h at room temperature. The solvent is concentrated and the residue is diluted by CH2Cl2 and H2O. The layers are separated and the organic extract is washed successively with H2O and brine. The combined organic layers are dried with MgSO4, filtered and concentrated. The crude material is purified by flash chromatography on silica gel (eluent: CH2Cl2/MeOH 95:5) to give the title product. TLC, Rf (AcOEt)=0.23. MS (LC-MS): 363.3 [M+H]+; tR (HPLC, C18 column, 10-100% CH3CN/H2O/5 min, 100% CH3CN/2.5 min, CH3CN and H2O containing 0.1% TFA, flow: 1.5 mL/min): 5.06 min.

Workup

  1. concentrationThe solvent is concentrated
  2. additionthe residue is diluted by CH2Cl2 and H2O
  3. customThe layers are separated
  4. extractionthe organic extract
  5. washis washed successively with H2O and brine
  6. dry with materialThe combined organic layers are dried with MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude material is purified by flash chromatography on silica gel (eluent: CH2Cl2/MeOH 95:5)

Sources & evidence

ORD record
ord-37d93d7c29f546498df4cfc298b89eec
Source dataset
uspto-grants-2010_10
Patent number
US07807709B2

Reaction notes

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