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

HRID 717869Notes

Reaction equation

HRID 717869 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) 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-799041f9b9724a8388cfa195b4f01efb
Source dataset
uspto-grants-2015_11
Patent number
US09193733B2

Reaction notes

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