Chloromethyl methyl sulfide → N-Tert-butoxycarbonyl-2(R,S)-methyl-4(S)-hydroxy-5(S)-amino-7(S)-isopropyl-8-[3-(methylthio-methoxy)-4-tert-butyl-phenyl]-octanoic acid (N-butyl)amide

HRID 725598Notes

Reaction equation

HRID 725598 reaction equation
[CH2:1]([NH:5][C:6](=[O:38])[CH:7]([CH3:37])[CH2:8][C@H:9]([OH:36])[C@@H:10]([NH:28][C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH2:11][C@@H:12]([CH:25]([CH3:27])[CH3:26])[CH2:13][C:14]1[CH:19]=[CH:18][C:17]([C:20]([CH3:23])([CH3:22])[CH3:21])=[C:16]([OH:24])[CH:15]=1)[CH2:2][CH2:3][CH3:4].[H-].[Na+].[CH3:41][S:42][CH2:43]Cl>CN(C)C=O>[CH2:1]([NH:5][C:6](=[O:38])[CH:7]([CH3:37])[CH2:8][C@H:9]([OH:36])[C@@H:10]([NH:28][C:29]([O:31][C:32]([CH3:34])([CH3:33])[CH3:35])=[O:30])[CH2:11][C@@H:12]([CH:25]([CH3:26])[CH3:27])[CH2:13][C:14]1[CH:19]=[CH:18][C:17]([C:20]([CH3:23])([CH3:22])[CH3:21])=[C:16]([O:24][CH2:41][S:42][CH3:43])[CH:15]=1)[CH2:2][CH2:3][CH3:4]

Participants

5

Reactant 3

HCID 16916Chloromethyl methyl sulfideHCID 24758Sodium hydrideHCID 54520950N-tert-butoxycarbonyl-2(R,S)-methyl-4(S)-hydroxy-5(S)-amino-7(S)-isopropyl-8-(3-hydroxy-4-tert-butyl-phenyl)-octanoic acid (N-butyl)amide

Product 1

HCID 131719569N-Tert-butoxycarbonyl-2(R,S)-methyl-4(S)-hydroxy-5(S)-amino-7(S)-isopropyl-8-[3-(methylthio-methoxy)-4-tert-butyl-phenyl]-octanoic acid (N-butyl)amide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Procedure

A solution of 100 mg of N-tert-butoxycarbonyl-2(R,S)-methyl-4(S)-hydroxy-5(S)-amino-7(S)-isopropyl-8-(3-hydroxy-4-tert-butyl-phenyl)-octanoic acid (N-butyl)amide (Example 5a) in 5 ml of dimethylformamide is added dropwise to a suspension, stirred at room temperature, of 7.6 mg of a 65% NaH dispersion in 3 ml of dimethylformamide. The reaction mixture is stirred for a further 30 minutes at more temperature and then a solution of 0.017 ml of chlorodimethyl sulfide in 2 ml of dimethylformamide is added thereto. The reaction mixture is stirred for a further 24 hours and then concentrated by evaporation. The residue is partitioned between ether and water. The organic phases are concentrated by evaporation and the title compound is obtained from the residue by FC (12 g of silica gel, dichloromethane/diethyl ether=2:1): Rf (dichloromethane/diethyl ether=2:1)=0.33.

Workup

  1. stirringThe reaction mixture is stirred for a further 24 hours
  2. concentrationconcentrated by evaporation
  3. customThe residue is partitioned between ether and water
  4. concentrationThe organic phases are concentrated by evaporation

Sources & evidence

ORD record
ord-3752eef0896649ffbcf2d2919b30be3a
Source dataset
uspto-grants-1998_01
Patent number
US05705658

Reaction notes

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