tert-Butanol → 4-chloro-2-({[(1,1-dimethylethyl)(dimethyl)silyl]oxy}methyl)-1-({[2-(trimethylsilyl)ethyl]oxy}methyl)-1H-imidazole-5-carboxylic acid

HRID 1875121Notes

Reaction equation

HRID 1875121 reaction equation
[O-]Cl=O.[Na+].[Cl:5][C:6]1[N:7]=[C:8]([CH2:21][O:22][Si:23]([C:26]([CH3:29])([CH3:28])[CH3:27])([CH3:25])[CH3:24])[N:9]([CH2:13][O:14][CH2:15][CH2:16][Si:17]([CH3:20])([CH3:19])[CH3:18])[C:10]=1[CH:11]=[O:12].CC(=CC)C.CC([OH:39])(C)C>O.C1COCC1>[Cl:5][C:6]1[N:7]=[C:8]([CH2:21][O:22][Si:23]([C:26]([CH3:29])([CH3:28])[CH3:27])([CH3:25])[CH3:24])[N:9]([CH2:13][O:14][CH2:15][CH2:16][Si:17]([CH3:20])([CH3:19])[CH3:18])[C:10]=1[C:11]([OH:39])=[O:12]

Participants

7

Reactant 4

HCID 6386tert-ButanolHCID 105532-Methyl-2-buteneHCID 23668197Sodium ChloriteHCID 715339744-Chloro-2-({[(1,1-dimethylethyl)(dimethyl)silyl]oxy}methyl)-1-({[2-(trimethylsilyl)ethyl]oxy}methyl)-1H-imidazole-5-carbaldehyde

Product 1

HCID 684865744-chloro-2-({[(1,1-dimethylethyl)(dimethyl)silyl]oxy}methyl)-1-({[2-(trimethylsilyl)ethyl]oxy}methyl)-1H-imidazole-5-carboxylic acidYield 99%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of NaClO2 (1.55 g, 17 mmol) and NaH2PO4 H2O (1.42 g, 10.3 mmol) in H2O was added to a mixture of 4-chloro-2-({[(1,1-dimethylethyl)(dimethyl)silyl]oxy}methyl)-1-({[2-(trimethylsilyl)ethyl]oxy}methyl)-1H-imidazole-5-carbaldehyde (694 mg, 1.7 mmol), 2-methyl-2-butene (10.8 mL, 21.5 mmol, 2 M in THF), and tBuOH (1.33 mL) in THF (5.5 mL) at room temperature. The mixture was stirred overnight and separated and the aqueous layer was extracted with EtOAc. The combined extracts were dried over sodium sulfate and concentrated. The residue was purified by column chromatography (0-80% 0.1%) formic acid solution of EtOAc in DCM) to give the title compound (740 mg, >99%) as a white solid. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 5.83 (2H, s) 4.80 (2H, s) 3.56 (2H, t, J=8.1 Hz) 0.83-0.91 (11H, m) 0.08 (6H, s) −0.04 (9H, s). LCMS: m/z 421 (M+1).

Workup

  1. customseparated
  2. extractionthe aqueous layer was extracted with EtOAc
  3. dry with materialThe combined extracts were dried over sodium sulfate
  4. concentrationconcentrated
  5. customThe residue was purified by column chromatography (0-80% 0.1%) formic acid solution of EtOAc in DCM)

Sources & evidence

ORD record
ord-623bd04128b84bb9846a6fd42db7e2fd
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

Loading…