Sodium Iodide → (2S)-2-benzyloxycarbonylamino-4-methyl-pentanoic acid 3-methyloxetan-3-ylmethyl ester

HRID 1009302Notes

Reaction equation

HRID 1009302 reaction equation
[C:1]([NH:11][C@H:12]([C:17]([OH:19])=[O:18])[CH2:13][CH:14]([CH3:16])[CH3:15])([O:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:2].C([O-])([O-])=O.[Cs+].[Cs+].[CH3:26][C:27]1([CH2:31]OS(C2C(C)=CC=CC=2)(=O)=O)[CH2:30][O:29][CH2:28]1.[Na+].[I-]>O.CN(C=O)C>[CH3:26][C:27]1([CH2:31][O:18][C:17](=[O:19])[C@@H:12]([NH:11][C:1]([O:3][CH2:4][C:5]2[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=2)=[O:2])[CH2:13][CH:14]([CH3:16])[CH3:15])[CH2:30][O:29][CH2:28]1

Participants

7

Reactant 4

HCID 5238Sodium IodideHCID 10796Cesium carbonateHCID 74840Leucine, N-carboxy-, N-benzyl ester, L-HCID 534258303-Methyl-3-(toluenesulfonyl-oxymethyl)oxetane

Product 1

HCID 67298758(2S)-2-benzyloxycarbonylamino-4-methyl-pentanoic acid 3-methyloxetan-3-ylmethyl ester

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

Cbz-L-leucine (2 g, 7.5 mmol) and Cs2CO3 (1.46 g, 4.5 mmol, 0.6 eq) were dissolved in water (20 mL). Water was then removed in vacuo, and the resulting oil was lyophilized for 12 h to give a white solid. To this solid were added 3-methyl-3-(toluenesulfonyl-oxymethyl)oxetane (oxetane tosylate) (1.8 g, 4.5 mmol), and NaI (224 mg, 1.5 mmol, 0.2 eq.) which were taken up in DMF (35 mL) and allowed to stir under nitrogen for 48 h. The DMF was then removed in vacuo, and the resulting solid was dissolved in EtOAc (60 mL) and washed with 10% NaHCO3 (20 mL) and saturated NaCl (10 mL) and dried over MgSO4. The solvent was removed under reduced pressure to yield yellow oil which was flash column chromatographed on 200 cm3 of silica gel using 3:1 hexanes:EtOAc as an eluant to give (2S)-2-benzyloxycarbonylamino-4-methyl-pentanoic acid 3-methyloxetan-3-ylmethyl ester (Cbz-Leu oxetane ester) as a yellow thick oil.

Workup

  1. customWater was then removed in vacuo
  2. customto give a white solid
  3. customThe DMF was then removed in vacuo
  4. dissolutionthe resulting solid was dissolved in EtOAc (60 mL)
  5. washwashed with 10% NaHCO3 (20 mL) and saturated NaCl (10 mL)
  6. dry with materialdried over MgSO4
  7. customThe solvent was removed under reduced pressure
  8. customto yield yellow oil which
  9. customchromatographed on 200 cm3 of silica gel using 3:1 hexanes

Sources & evidence

ORD record
ord-e45cf123f9904c33b2bec85016ac9173
Source dataset
uspto-grants-2011_07
Patent number
US07973037B2

Reaction notes

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