Potassium Phosphate, Tribasic → HCID 178450652, compound

HRID 1849677Notes

Reaction equation

HRID 1849677 reaction equation
Cl[C:2]1[C:3]([O:16][CH2:17][C@H:18]2[CH2:23][CH2:22][C@H:21]([CH3:24])[CH2:20][CH2:19]2)=[CH:4][C:5]([F:15])=[C:6]([CH:14]=1)[C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8].[CH:25]1(B(O)O)[CH2:27][CH2:26]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.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH:25]1([C:2]2[C:3]([O:16][CH2:17][C@H:18]3[CH2:23][CH2:22][C@H:21]([CH3:24])[CH2:20][CH2:19]3)=[CH:4][C:5]([F:15])=[C:6]([CH:14]=2)[C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:27][CH2:26]1

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 2760897Cyclopropylboronic acidHCID 20066521Tri(cyclohexyl)phosphine tetrafluoroborateHCID 178450706HCID 178450706, compound

Product 1

HCID 178450652HCID 178450652, compoundYield 90.4%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 22272177Toluene waterSolvent

Conditions

Temperature
110 °C

Procedure

To a solution of tert-butyl 5-chloro-2-fluoro-4-((trans-4-methylcyclohexyl)-methoxy)-benzoate (6.48 g, 18.16 mmol) in toluene-water (40 mL, v/v 20:1) was added cyclopropylboronic acid (2.34 g, 27.26 mmol) and tribasic potassium phosphate (17.37, 81.84 mmol). The reaction mixture was sparged with argon for 10 minutes and then charged with tricyclohexylphosphine tetrafluoroborate (1.35 g, 3.67 mmol) and palladium acetate (0.41 g, 1.82 mmol). The mixture was heated at 110° C. for 72 hours, then cooled to ambient temperature; filtered through a pad of diatomaceous earth and washed with ethyl acetate. The filtrate was concentrated in vacuo, and the residue was purified by column chromatography (0% to 10% ethyl acetate) to give the title compound (5.95 g, 90%): 1H NMR (300 MHz, CDCl3) δ 7.37 (d, J=8.4 Hz, 1H), 6.50 (d, J=12.8 Hz, 1H), 3.78 (d, J=6.1 Hz, 2H), 1.91-1.70 (m, 8H), 1.56 (s, 9H), 1.41-129 (m, 2H), 1.14-0.95 (m, 6H), 0.65-0.60 (m, 2H).

Workup

  1. customThe reaction mixture was sparged with argon for 10 minutes
  2. temperaturecooled to ambient temperature
  3. filtrationfiltered through a pad of diatomaceous earth
  4. washwashed with ethyl acetate
  5. concentrationThe filtrate was concentrated in vacuo
  6. customthe residue was purified by column chromatography (0% to 10% ethyl acetate)

Sources & evidence

ORD record
ord-ab9be3793d3f4007afc95de0f1e86e19
Source dataset
uspto-grants-2015_02
Patent number
US08952169B2

Reaction notes

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