Imidazole → (1S)-[1-(tert-Butyldimethylsilanyloxymethyl)-3-(tritylcarbamoyl)propyl]carbamic Acid Benzyl Ester

HRID 1057749Notes

Reaction equation

HRID 1057749 reaction equation
[CH2:1]([O:8][C:9](=[O:38])[NH:10][C@H:11]([CH2:36][OH:37])[CH2:12][CH2:13][C:14](=[O:35])[NH:15][C:16]([C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)([C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.N1C=CN=C1.[Si:44](Cl)([C:47]([CH3:50])([CH3:49])[CH3:48])([CH3:46])[CH3:45]>CN(C=O)C.CC(OC)(C)C>[CH2:1]([O:8][C:9](=[O:38])[NH:10][C@H:11]([CH2:36][O:37][Si:44]([C:47]([CH3:50])([CH3:49])[CH3:48])([CH3:46])[CH3:45])[CH2:12][CH2:13][C:14](=[O:35])[NH:15][C:16]([C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1)([C:29]1[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 10505827(1S)-[1-Hydroxymethyl-3-(tritylcarbamoyl)propyl]carbamic Acid Benzyl Ester

Product 1

HCID 70029215(1S)-[1-(tert-Butyldimethylsilanyloxymethyl)-3-(tritylcarbamoyl)propyl]carbamic Acid Benzyl EsterYield 71%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 15413tert-Butyl methyl etherSolvent

Procedure

Intermediate B1, prepared above, was dissolved in DMF (10 mL). Imidazole (2.69 g, 39.5 mmol, 2.3 equiv) and tert-butyldimethylsilyl chloride (2.86 g, 19.0 mmol, 1.1 equiv) were added. The reaction mixture was stirred overnight, then diluted with MTBE (500 mL) and washed sequentially with 2.5% KHSO4, H2O, NaHCO3, H2O, and brine (100 mL each). The organic phase was dried over MgSO4 and evaporated. The residue was purified by flash column chromatography (gradient elution, 25→40% EtOAc in hexanes) to provide the title intermediate (7.6 g, 71%) as a white amorphous solid: IR (cm−1) 3307, 1708, 1660, 1496, 1249; 1H NMR (CDCl3) δ-0.01-0.05 (m, 6H), 0.89 (s, 9H), 1.76-1.93 (m. 2H), 2.29-2.40 (m, 2H), 3.56-3.77 (m, 3H), 5.03-5.16 (m, 3H), 7.00 (s, 1H), 7.18-7.39 (m, 20 H); Anal. C38H46N2O4Si: C, H, N.

Workup

  1. washwashed sequentially with 2.5% KHSO4, H2O, NaHCO3, H2O, and brine (100 mL each)
  2. dry with materialThe organic phase was dried over MgSO4
  3. customevaporated
  4. customThe residue was purified by flash column chromatography (gradient elution, 25→40% EtOAc in hexanes)

Sources & evidence

ORD record
ord-41beebf3b0354f0da402e742ec43f839
Source dataset
uspto-grants-2003_02
Patent number
US06514997B2

Reaction notes

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