Potassium Phosphate, Tribasic → Methyl 6-(adamantan-1-ylmethoxy)-5-cyclopropylnicotinate

HRID 1849580Notes

Reaction equation

HRID 1849580 reaction equation
[C:1]12([CH2:11][O:12][C:13]3[C:22](Cl)=[CH:21][C:16]([C:17]([O:19][CH3:20])=[O:18])=[CH:15][N:14]=3)[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2.[CH:24]1(B(O)O)[CH2:26][CH2:25]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].F[B-](F)(F)F.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:1]12([CH2:11][O:12][C:13]3[C:22]([CH:24]4[CH2:26][CH2:25]4)=[CH:21][C:16]([C:17]([O:19][CH3:20])=[O:18])=[CH:15][N:14]=3)[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 2760897Cyclopropylboronic acidHCID 20066521Tri(cyclohexyl)phosphine tetrafluoroborateHCID 86702922Methyl 6-(adamantan-1-ylmethoxy)-5-chloronicotinate

Product 1

HCID 86702923Methyl 6-(adamantan-1-ylmethoxy)-5-cyclopropylnicotinateYield 89.2%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Procedure

A mixture of methyl 6-(adamantan-1-ylmethoxy)-5-chloronicotinate (1.29 g, 3.84 mmol), cyclopropylboronic acid (0.43 g, 4.99 mmol), potassium phosphate (3.26 g, 15.40 mmol), tricyclohexylphosphine tetrafluoroborate (0.14 g, 0.38 mmol) and palladium acetate (0.04 g, 0.19 mmol) in degassed toluene (50 mL) and degassed water (5 mL) was refluxed under nitrogen for 7 h. The reaction mixture was cooled to ambient temperature and diluted with ethyl acetate (100 mL), washed with water (50 mL), saturated ammonium chloride (50 mL) and brine (50 mL); dried over anhydrous sodium sulfate, filtered through diatomaceous earth and concentrated in vacuo. The residue was purified by flash chromatography eluting with 5% ethyl acetate in hexanes to afford the title compound as a white solid (1.17 g, 89%); 1H NMR (300 MHz, CDCl3) δ 8.57 (d, J=2.2 Hz, 1H), 7.67 (d, J=2.2 Hz, 1H), 3.95 (s, 2H), 3.85 (s, 3H), 2.09-1.96 (m, 4H), 1.78-1.63 (m, 12H), 0.99-0.91 (m, 2H), 0.72-0.65 (m, 2H); MS (ES+) m/z: 342.22 (M+1).

Workup

  1. customdegassed water (5 mL)
  2. temperaturewas refluxed under nitrogen for 7 h
  3. additiondiluted with ethyl acetate (100 mL)
  4. washwashed with water (50 mL), saturated ammonium chloride (50 mL) and brine (50 mL)
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered through diatomaceous earth
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by flash chromatography
  9. washeluting with 5% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-8658e8db551547148245fb9cf250e4e4
Source dataset
uspto-grants-2015_02
Patent number
US08952169B2

Reaction notes

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