Imidazole → 4-({[tert-Butyl(diphenyl)silyl]oxy}methyl)-2-chloro-6-(trifluoromethyl)pyridine

HRID 1426337Notes

Reaction equation

HRID 1426337 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([CH2:8][OH:9])[CH:5]=[C:4]([C:10]([F:13])([F:12])[F:11])[N:3]=1.N1C=CN=C1.[C:19]([Si:23](Cl)([C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)([CH3:22])([CH3:21])[CH3:20]>C(Cl)Cl.CN(C)C1C=CN=CC=1.C(OCC)C>[Si:23]([O:9][CH2:8][C:6]1[CH:5]=[C:4]([C:10]([F:11])([F:12])[F:13])[N:3]=[C:2]([Cl:1])[CH:7]=1)([C:19]([CH3:22])([CH3:21])[CH3:20])([C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1

Participants

7

Reactant 3

HCID 795ImidazoleHCID 94078tert-ButyldiphenylchlorosilaneHCID 722125832-Chloro-6-(trifluoromethyl)-4-pyridinemethanol

Product 1

HCID 866665034-({[tert-Butyl(diphenyl)silyl]oxy}methyl)-2-chloro-6-(trifluoromethyl)pyridine

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of [2-chloro-6-(trifluoromethyl)pyridin-4-yl]methanol (142 mg, 0.671 mmol, Example 121, Step A) in methylene chloride (1.0 mL) at 0° C. was added 1H-imidazole (55 mg, 0.80 mmol) followed by tert-Butylchlorodiphenylsilane (190 μL, 0.74 mmol) and 4-dimethylaminopyridine (4 mg, 0.03 mmol). The reaction was stirred with warming to room temperature for 64 hours. The reaction mixture was diluted with diethyl ether and was washed with water followed by brine, dried over sodium sulfate, decanted and concentrated. Flash chromatography on silica gel, eluting with a gradient from 0-4% EtOAc in hexanes afforded product as a white solid (0.20 g, 66%). 1H NMR (300 MHz, CDCl3) δ 7.70-7.58 (m, 4H), 7.55-7.34 (m, 8H), 4.77 (s, 2H), 1.12 (s, 9H); 19F NMR (282 MHz, CDCl3) δ−68.49 (s); LCMS (M+H)+: 450.1.

Workup

  1. washwas washed with water
  2. dry with materialdried over sodium sulfate
  3. customdecanted
  4. concentrationconcentrated
  5. washFlash chromatography on silica gel, eluting with a gradient from 0-4% EtOAc in hexanes afforded product as a white solid (0.20 g, 66%)

Sources & evidence

ORD record
ord-97e84094454f48b98450a2fa7982c7c2
Source dataset
uspto-grants-2015_01
Patent number
US08933085B2

Reaction notes

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