Hydrochloric Acid → 1-Pyrrolidinecarboxylic acid, 2-(hydroxymethyl)-5-phenyl-, 1,1-dimethylethyl ester, (2S,5R)-

HRID 354439Notes

Reaction equation

HRID 354439 reaction equation
[C:1]([N:8]1[C@@H:15]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH2:14][CH2:13][C@H:9]1[C:10](O)=[O:11])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].S(C)C.Cl>C1COCC1>[C:1]([N:8]1[C@@H:15]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH2:14][CH2:13][C@H:9]1[CH2:10][OH:11])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 1068Dimethyl SulfideHCID 2755972(2S,5R)-1-[(tert-butoxy)carbonyl]-5-phenylpyrrolidine-2-carboxylic acid

Product 1

HCID 207378581-Pyrrolidinecarboxylic acid, 2-(hydroxymethyl)-5-phenyl-, 1,1-dimethylethyl ester, (2S,5R)-Yield 102.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of N-Boc-5-(R)-phenyl-(2S)-proline (1.14 g, 3.91 mmol) in THF (20 ml) was added 10M-BH3.Me2S (780 ml, 7.82 mmol) at rt, and the resulting mixture was heated under reflux for 30 min. The mixture was poured into aq. 1N-HCl and extracted with EtOAc. The organic layer was dried over anhydrous Na2SO4, then concentrated in vacuo. The residue was chromatographed on silica gel with CHCl3—MeOH (10:1) as eluent to give N-Boc-2-(S)-hydroxymethyl-5-(R)-phenylpyrrolidine (1.11 g, quant.) as a colorless oil: 1H-NMR (CDCl3) δ1.19 (brs, 9 H), 1.65 (brs, 1 H), 1.83-1.90 (m, 1 H), 1.98-2.06 (m, 1 H), 2.22-2.31 (m, 1 H), 3.75-3.86 (m, 2 H), 4.16-4.19 (m, 1 H), 4.83 (t, J=6.8 Hz, 1 H), 4.89 (brs, 1 H), 7.19-7.31 (m, 5 H); MS (ESI) m/z, 2.78 (M++H).

Workup

  1. temperatureunder reflux for 30 min
  2. extractionextracted with EtOAc
  3. dry with materialThe organic layer was dried over anhydrous Na2SO4
  4. concentrationconcentrated in vacuo
  5. customThe residue was chromatographed on silica gel with CHCl3—MeOH (10:1) as eluent

Sources & evidence

ORD record
ord-c12a60d6ff3543b08f3bb6f068bb7f20
Source dataset
uspto-grants-2004_06
Patent number
US06756378B2

Reaction notes

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