Imidazole → HCID 67158968, compound

HRID 1892001Notes

Reaction equation

HRID 1892001 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([CH3:17])[CH2:13][CH:12]([CH2:14][OH:15])[CH2:11][CH2:10][CH:9]2[OH:16])=[CH:4][C:3]=1[C:18]([F:21])([F:20])[F:19].N1C=CN=C1.[C:27]([Si:31]([C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1)([C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)Cl)([CH3:30])([CH3:29])[CH3:28]>CN(C=O)C.C(OCC)(=O)C>[Si:31]([O:15][CH2:14][CH:12]1[CH2:11][CH2:10][CH:9]([OH:16])[C:8]([C:5]2[CH:6]=[CH:7][C:2]([Cl:1])=[C:3]([C:18]([F:19])([F:20])[F:21])[CH:4]=2)([CH3:17])[CH2:13]1)([C:27]([CH3:30])([CH3:29])[CH3:28])([C:39]1[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=1)[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1

Participants

6

Reactant 3

HCID 795ImidazoleHCID 94078tert-ButyldiphenylchlorosilaneHCID 67159214HCID 67159214, compound

Product 1

HCID 67158968HCID 67158968, compoundYield 73.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of (1RS,2RS,4RS)-2-(4-chloro-3-(trifluoromethyl)phenyl)-4-(hydroxymethyl)-2-methylcyclohexanol (1.253 g, 3.88 mmol) in DMF (15 mL) was treated with imidazole (0.581 g, 8.54 mmol) followed by tert-butyldiphenylchlorosilane (1.097 mL, 4.27 mmol). The resulting mixture was stirred at rt for 29 h. After this time, the solution was diluted with ethyl acetate (150 mL), washed three times with water, once with saturated aqueous sodium chloride, dried over sodium sulfate and concentrated under vacuum. The resulting residue was purified by column chromatography on silica gel, eluting with 5-25% ethyl acetate-hexanes, to provide (1RS,2RS,4RS)-4-((tert-butyldiphenylsilyloxy)methyl)-2-(4-chloro-3-(trifluoromethyl)phenyl)-2-methylcyclohexanol as a colorless gummy glass (1.599 g, 73%). 1H NMR (400 MHz, CDCl3) δ 8.14 (s, 1 H), 7.82 (dd, J=8.5, 1.6 Hz, 1 H), 7.63 (t, J=6.6 Hz, 4 H), 7.40 (m, 7 H), 3.72 (dt, J=12.0, 3.5, 3.4 Hz, 1 H), 3.42 (m, 2 H), 2.43 (m, 1 H), 1.69 (m, 5 H), 1.33 (s, 3 H), 1.12 (m, 2 H), 1.06 (s, 9 H).

Workup

  1. washwashed three times with water
  2. dry with materialonce with saturated aqueous sodium chloride, dried over sodium sulfate
  3. concentrationconcentrated under vacuum
  4. customThe resulting residue was purified by column chromatography on silica gel
  5. washeluting with 5-25% ethyl acetate-hexanes

Sources & evidence

ORD record
ord-fe9750be148140bc84c6079ae7e19aa4
Source dataset
uspto-grants-2013_08
Patent number
US08507559B2

Reaction notes

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