Methanol → N-(1-azabicyclo[2.2.2]oct-3-yl)-2-(4-ethynylphenyl)benzoxazole-4-carboxamide

HRID 969864Notes

Reaction equation

HRID 969864 reaction equation
[N:1]12[CH2:8][CH2:7][CH:4]([CH2:5][CH2:6]1)[CH:3]([NH:9][C:10]([C:12]1[CH:13]=[CH:14][CH:15]=[C:16]3[O:20][C:19]([C:21]4[CH:26]=[CH:25][C:24]([C:27]#[C:28][Si](C)(C)C)=[CH:23][CH:22]=4)=[N:18][C:17]=13)=[O:11])[CH2:2]2.C(=O)([O-])[O-].[K+].[K+].CO>C(OCC)(=O)C>[N:1]12[CH2:6][CH2:5][CH:4]([CH2:7][CH2:8]1)[CH:3]([NH:9][C:10]([C:12]1[CH:13]=[CH:14][CH:15]=[C:16]3[O:20][C:19]([C:21]4[CH:22]=[CH:23][C:24]([C:27]#[CH:28])=[CH:25][CH:26]=4)=[N:18][C:17]=13)=[O:11])[CH2:2]2

Participants

5

Reactant 3

HCID 887MethanolHCID 11430Potassium CarbonateHCID 11525069N-(1-azabicyclo[2.2.2]oct-3-yl)-2-(4-trimethylsilylethynylphenyl)benzoxazole-4-carboxamide

Product 1

HCID 11537988N-(1-azabicyclo[2.2.2]oct-3-yl)-2-(4-ethynylphenyl)benzoxazole-4-carboxamideYield 84%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

A mixture of N-(1-azabicyclo[2.2.2]oct-3-yl)-2-(4-trimethylsilylethynylphenyl)benzoxazole-4-carboxamide (20 mg, 0.045 mmol), potassium carbonate (20 mg, 0.14 mmol) and methanol (1 mL) was stirred at room temperature for 2 h, and then was diluted with ethyl acetate, washed with water and brine, dried (Na2SO4), filtered and concentrated. The crude material was purified by column chromatography (silica gel, 90:10:1 ethyl acetate/methanol/concentrated ammonium hydroxide) to afford N-(1-azabicyclo[2.2.2]oct-3-yl)-2-(4-ethynylphenyl)benzoxazole-4-carboxamide (14 mg, 84%) as a white solid: 1H NMR (500 MHz, CDCl3) δ 9.49 (d, J=7.0 Hz, 1H), 8.22-8.18 (m, 3H), 7.73 (dd, J=8.0, 1.0 Hz, 1H), 7.68 (d, J=8.5 Hz, 2H), 7.48 (t, J=8.0 Hz, 1H), 4.35-4.31 (m, 1H), 3.53 (ddd, J=14.0, 9.5, 2.0 Hz, 1H), 3.30 (s, 1H), 3.15-2.82 (m, 5H), 2.20-2.03 (m, 2H), 1.80-1.62 (m, 3H); MS (ESI+) m/z 372 (M+H); HPLC>99% (AUC), tR=12.77 min.

Workup

  1. washwashed with water and brine
  2. dry with materialdried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe crude material was purified by column chromatography (silica gel, 90:10:1 ethyl acetate/methanol/concentrated ammonium hydroxide)

Sources & evidence

ORD record
ord-35d90bc8c32c45299cc5a746e61c958c
Source dataset
uspto-grants-2007_12
Patent number
US07307094B2

Reaction notes

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