Potassium Phosphate, Tribasic → HCID 59442643, compound

HRID 657502Notes

Reaction equation

HRID 657502 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:8]2([O:23][CH2:24][CH:25]3[CH2:27][CH2:26]3)[CH2:13][CH2:12][C:11]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)([C:14]([OH:16])=[O:15])[CH2:10][CH2:9]2)[CH:5]=[CH:6][CH:7]=1.[CH:28]1(B(O)O)[CH2:30][CH2:29]1.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C1(C)C=CC=CC=1.O.CC(=O)OCC.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH:25]1([CH2:24][O:23][C:8]2([C:4]3[CH:5]=[CH:6][CH:7]=[C:2]([CH:28]4[CH2:30][CH2:29]4)[CH:3]=3)[CH2:9][CH2:10][C:11]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)([C:14]([OH:16])=[O:15])[CH2:12][CH2:13]2)[CH2:27][CH2:26]1

Participants

9

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 2760897Cyclopropylboronic acidHCID 59442638HCID 59442638, compound

Product 1

HCID 59442643HCID 59442643, compoundYield 14.5%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

190 mg of 4-(3-bromophenyl)-4-cyclopropylmethoxy-1-phenylcyclohexanecarboxylic acid, 57 mg of cyclopropylboronic acid, 12.4 mg of tricyclohexylphosphine, 4.97 mg of palladium(II) acetate and 376 mg of potassium phosphate (K3PO4) were heated for 4 h at 100° C. in 10 ml of toluene and 1 ml of water. The reaction mixture was allowed to stand for 15 h at room temperature and subsequently heated for a further 3 h at 100° C. It was then diluted with 50 ml of EA and washed twice with 20 ml each of a saturated aqueous sodium hydrogensulfate solution. The organic phase was dried over magnesium sulfate and the solvent was removed in vacuo. The residue was purified by preparative HPLC (column: Waters X-Terra MS C18, 100×30 mm, 5 μm; eluent A: water+0.1% TFA, eluent B: acetonitrile; flow: 30 ml/min; gradient: 90% A+10% B for 2.5 min, then to 75% A+25% B in 0.5 min, then to 25% A+75% B in 11 min, then to 5% A+95% B in 1 min, then to 90% A+10% B in 2.5 min). 25 mg of the title compound were obtained as an amorphous solid.

Workup

  1. washwashed twice with 20 ml each of a saturated aqueous sodium hydrogensulfate solution
  2. dry with materialThe organic phase was dried over magnesium sulfate
  3. customthe solvent was removed in vacuo
  4. customThe residue was purified by preparative HPLC (column
  5. waitgradient: 90% A+10% B for 2.5 min
  6. waitto 75% A+25% B in 0.5 min
  7. waitto 25% A+75% B in 11 min
  8. waitto 5% A+95% B in 1 min
  9. waitto 90% A+10% B in 2.5 min)

Sources & evidence

ORD record
ord-d8a29665707c48598b5e4fbe767b590c
Source dataset
uspto-grants-2011_12
Patent number
US08076324B2

Reaction notes

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