Water → HCID 131725930, compound

HRID 2213141Notes

Reaction equation

HRID 2213141 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[CH2:9][CH2:10][CH2:11][O:12][C:13]1[C:14]2[N:15]([C:19]([C:26](OCC)=[O:27])=[C:20]([C:22]([F:25])([F:24])[F:23])[N:21]=2)[CH:16]=[CH:17][CH:18]=1.B.[OH-].[Na+].O>C(OCC)C>[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[CH2:9][CH2:10][CH2:11][O:12][C:13]1[C:14]2[N:15]([C:19]([CH2:26][OH:27])=[C:20]([C:22]([F:24])([F:23])[F:25])[N:21]=2)[CH:16]=[CH:17][CH:18]=1

Participants

6

Reactant 4

HCID 962WaterHCID 6331BoraneHCID 14798Sodium HydroxideHCID 70245760HCID 70245760, compound

Product 1

HCID 131725930HCID 131725930, compoundYield 47%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

To a stirred solution of ethyl 8-[3-(2,4-dichlorophenyl)propoxy]-2-(trifluoro-methyl)imidazo[1,2-α]pyridine-3-carboxylate (0.223 g, 0.483 mmol, see example 35) in anhydrous diethyl ether (20 mL) was added dropwise borane-methyl sulfide complex (2.0 mL, 20 mmol). The reaction mixture was stirred at ambient temperature for 42 h under argon and then heated at reflux for 3.5 h. Excess borane was subsequently hydrolyzed by dropwise addition of 5M aq sodium hydroxide (4 mL) to the cold (0° C.) reaction mixture. The resultant solution was stirred for 30 min and water (50 mL) was added. After successive extraction of the solution with diethyl ether (2×30 mL) and dichloromethane (30 mL), the organic extracts were combined, dried over anhydrous sodium sulfate and concentrated in vacuo to yield the crude desired product as a white solid. Purification by chromatography with a mixture of ethyl acetate-hexanes (1:1 v/v, containing 0.5% v/v isopropylamine) yielded 94.3 mg (47% yield) of {8-[3-(2,4-dichlorophenyl)propoxy]-2-(trifluoromethyl)imidazo[1,2-α]pyridin-3-yl}methanol as a pale yellow solid (Rf=0.41 in ethyl acetate-hexanes, 1:1 v/v, containing 0.5% v/v isopropylamine). A stirred suspension of {8-[3-(2,4-dichlorophenyl)propoxy]-2-(trifluoromethyl)imidazo[1,2-α]pyridin-3-yl}methanol (0.142 g, 0.339 mmol) in anhydrous methanol (5 mL) was treated with ethereal hydrogen chloride to form the hydrochloride salt. Concentration of the solution in vacuo and trituration of the residue in anhydrous diethyl ether afforded the title compound as an off-white solid (0.144 g, 93% yield). 1H-NMR (400 MHz, CDCl3/CD3OD) δ 8.46 (d, 1H, Ar), 7.39–7.45 (m, 2H, Ar), 7.35 (d, 1H, Ar), 7.27 (d, 1H, Ar), 7.19 (dd, 1H, Ar), 5.09 (s, 2H, CH2OH), 4.36 (t, 2H, CH2O), 2.99 (t, 2H, CH2Ar), 2.26 (m, 2H, CH2CH2CH2); 13C-NMR (100 MHz, CDCl3/CD3OD, APT) δ 146.38 (+), 138.09 (+), 136.58 (+), 135.35 (+), 133.50 (+), 132.24 (−), 129.94 (−), 128.28 (+), 128.06 (−), 124.01 (+), 122.05/119.36 (+), 120.49 (−), 119.12 (−), 112.57 (−), 70.26 (+), 52.25 (+), 29.76 (+), 29.10 (+); LRMS-ES m/z: M+ 419.2 (100%); Anal. calcd for C18H15N2O2Cl2F3.HCl: C, 47.44; H, 3.54; N, 6.15%. found: C, 47.04; H, 3.54; N, 6.02%.

Workup

  1. temperatureheated
  2. temperatureat reflux for 3.5 h
  3. extractionAfter successive extraction of the solution with diethyl ether (2×30 mL) and dichloromethane (30 mL)
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customto yield the crude desired product as a white solid
  7. customPurification by chromatography
  8. additionwith a mixture of ethyl acetate-hexanes (1:1 v/v
  9. additioncontaining 0.5% v/v isopropylamine)

Sources & evidence

ORD record
ord-88ceba6ee5fe4e309c89273c3fa24dc5
Source dataset
uspto-grants-2006_09
Patent number
US07105534B2

Reaction notes

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