Sodium Iodide → 2(S)-benzyloxycarbonylamino-4,4-dimethylpentanoic acid 3-methyloxetan-3-ylmethyl ester

HRID 907615Notes

Reaction equation

HRID 907615 reaction equation
[CH3:1][C:2]1([CH2:6]OS(C2C=CC(C)=CC=2)(=O)=O)[CH2:5][O:4][CH2:3]1.C(=O)([O-])[O-].[Cs+].[Cs+].[CH2:24]([O:31][C:32]([NH:34][C@@H:35]([CH2:39][C:40]([CH3:43])([CH3:42])[CH3:41])[C:36]([OH:38])=[O:37])=[O:33])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.[I-].[Na+]>O.CN(C=O)C.C(OCC)(=O)C>[CH3:1][C:2]1([CH2:6][O:37][C:36](=[O:38])[C@@H:35]([NH:34][C:32]([O:31][CH2:24][C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=2)=[O:33])[CH2:39][C:40]([CH3:43])([CH3:42])[CH3:41])[CH2:5][O:4][CH2:3]1

Participants

8

Reactant 4

HCID 5238Sodium IodideHCID 10796Cesium carbonateHCID 5461213(3-Methyloxetan-3-yl)methyl 4-methylbenzenesulfonateHCID 70202524-Methyl-N-((phenylmethoxy)carbonyl)-L-leucine

Product 1

HCID 673918222(S)-benzyloxycarbonylamino-4,4-dimethylpentanoic acid 3-methyloxetan-3-ylmethyl esterYield 89.6%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Toluene-4-sulfonic acid 3-methyloxetan-3-ylmethyl ester (18.6 g, 66 mmol) was added to a solution of cesium carbonate (13.04 g, 39 mmol) in water (15 ml) and stirred until the solution became clear. The solution was lyophilized overnight to give flaky white solid. The solid was dissolved in DMF (50 ml) and 2(S)-benzyloxycarbonylamino-4,4-dimethylpentanoic acid (15.99 g, 66 mmol) and sodium iodide (2 g, 13.2 mmol) were added. After 48 h, the solution was diluted with 500 ml of ethyl acetate, washed with water, saturated solution of sodium bicarbonate solution (50 ml) and brine. The ethyl acetate layer was separated and dried over MgSO4. The solvent was evaporated and the crude was column chromatographed on a silica gel column using 20:80 EtOAc:Hexane as eluent to give 2(S)-benzyloxycarbonylamino-4,4-dimethylpentanoic acid 3-methyloxetan-3-ylmethyl ester (21.5 g) as a white solid.

Workup

  1. customto give flaky white solid
  2. waitAfter 48 h
  3. washwashed with water, saturated solution of sodium bicarbonate solution (50 ml) and brine
  4. customThe ethyl acetate layer was separated
  5. dry with materialdried over MgSO4
  6. customThe solvent was evaporated
  7. customchromatographed on a silica gel column

Sources & evidence

ORD record
ord-9de4de9080bd4bc3b358f416417ba9ed
Source dataset
uspto-grants-2011_09
Patent number
US08013186B2

Reaction notes

Loading…