Methyl iodide → HCID 16093620, compound

HRID 354428Notes

Reaction equation

HRID 354428 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][C@@H:11]([OH:13])[CH2:10][C@H:9]1[CH2:14][O:15][C:16]1[CH:25]=[CH:24][C:19]([C:20]([O:22][CH3:23])=[O:21])=[CH:18][CH:17]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[CH3:28]I>C1COCC1>[C:1]([O:5][C:6]([N:8]1[CH2:12][C@@H:11]([O:13][CH3:28])[CH2:10][C@H:9]1[CH2:14][O:15][C:16]1[CH:17]=[CH:18][C:19]([C:20]([O:22][CH3:23])=[O:21])=[CH:24][CH:25]=1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 6328Methyl iodide2×HCID 24758Sodium hydride2×HCID 16093638methyl 4-[(2S,4S)-1-tert-butoxycarbonyl-4-hydroxy-2-pyrrolidinyl]methoxybenzoate

Product 1

HCID 16093620HCID 16093620, compoundYield 60.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of methyl 4-[(2S,4S)-1-tert-butoxycarbonyl-4-hydroxy-2-pyrrolidinyl]methoxybenzoate (2.10 g, 5.98 mmol) in THF (60 ml) was added 60% oil NaH (359 mg, 8.97 mmol) at 0° C. After 15 minutes stirring, MeI (1.20 ml, 8.97 mmol) was added to the mixture was added at same temperature, and the resulting mixture was allowed to raise to room temperature for over 1 h. Then 60% oil NaH (359 mg, 8.97 mmol) and MeI (1.20 ml, 8.97 mmol) was added to the reaction mixture at room temperature and stirred for 14 h. The reaction mixture was poured into ice water and extracted with CHCl3. The combined extracts were washed with aq. NaHCO3 and brine. After dried over Na2SO4, the extracts were concentrated in vacuo. The residue was chromatographed on silica gel [50 g, n-hexane/EtOAc(4/1)], to give methyl 4-[(2S,4S)-1-tert-butoxycarbonyl-4-methoxy-2-pyrrolidinyl]methoxybenzoate (1.32 g, 60%) as a colorless oil. 1H-NMR (CDCl3) δ1.48 (s, 9H), 2.05 (m, 1H), 2.29 (d, J=14.2 Hz, 1H), 3.30 (s, 3H), 3.36-4.38 (m, 4H), 6.76 (br, 2H), 7.97 (d, J=8.8 Hz, 2H).

Workup

  1. additionwas added at same temperature
  2. stirringstirred for 14 h
  3. extractionextracted with CHCl3
  4. washThe combined extracts were washed with aq. NaHCO3 and brine
  5. dry with materialAfter dried over Na2SO4
  6. concentrationthe extracts were concentrated in vacuo
  7. customThe residue was chromatographed on silica gel [50 g, n-hexane/EtOAc(4/1)]

Sources & evidence

ORD record
ord-f041bfb96b8e4b6badf4f0b9a246f184
Source dataset
uspto-grants-2004_06
Patent number
US06756378B2

Reaction notes

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