Potassium Carbonate → HCID 86718779, compound

HRID 1854216Notes

Reaction equation

HRID 1854216 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:16]2[CH:21]=[CH:20][C:19]([Cl:22])=[C:18]([Cl:23])[CH:17]=2)[C:5]2[O:10]C[N:8]([C:11]([CH3:14])([CH3:13])[CH3:12])[CH2:7][C:6]=2[CH:15]=1.[F:24][C:25]([F:36])([F:35])[C:26]1[N:31]=[CH:30][C:29](B(O)O)=[CH:28][CH:27]=1.C(=O)([O-])[O-].[K+].[K+]>COCCOCCOC.O>[C:11]([NH:8][CH2:7][C:6]1[CH:15]=[C:2]([C:29]2[CH:30]=[N:31][C:26]([C:25]([F:36])([F:35])[F:24])=[CH:27][CH:28]=2)[CH:3]=[C:4]([C:16]2[CH:21]=[CH:20][C:19]([Cl:22])=[C:18]([Cl:23])[CH:17]=2)[C:5]=1[OH:10])([CH3:14])([CH3:12])[CH3:13]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 251342782-(Trifluoromethyl)pyridine-5-boronic AcidHCID 86718780HCID 86718780, compound

Product 1

HCID 86718779HCID 86718779, compoundYield 15.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8150DiglymeSolvent

Conditions

Temperature
68 °C

Procedure

A mixture of 6-bromo-3-(tert-butyl)-8-(3,4-dichlorophenyl)-3,4-dihydro-2H-benzo[e][1,3]oxazine (0.743 g, 1.80 mmol), (6-(trifluoromethyl)pyridin-3-yl)boronic acid (0.685 g, 2.0 equiv), and potassium carbonate (0.995 g, 4 equiv) in 2-methoxyethyl ether (32 mL) and water (6.5 mL) was purged with nitrogen for 20 minutes. Tetrakis(triphenylphosphine)Pd (0) (0.120 g, 5.8 mol %) was added and the resulting mixture was heated at 65-71° C. for 2 hours. The cooled reaction mixture was concentrated and the resulting residue was purified by column chromatograph to give 3-((tert-butylamino)methyl)-3′,4′-dichloro-5-(6-(trifluoromethyl)pyridine-3-yl)-[1,1′-biphenyl]2-ol (0.128 g). The free base was dissolved in methanol, and to the solution 37% HCl was added. The resulting solid was filtered and rinsed with ethyl acetate to give 3-((tert-butylamino)methyl)-3′,4′-dichloro-5-(6-(trifluoromethyl)pyridine-3-yl)-[1,1′-biphenyl]2-ol hydrochloride (0.126 g).

Workup

  1. customwas purged with nitrogen for 20 minutes
  2. additionTetrakis(triphenylphosphine)Pd (0) (0.120 g, 5.8 mol %) was added
  3. customThe cooled reaction mixture
  4. concentrationwas concentrated
  5. customthe resulting residue was purified by column chromatograph

Sources & evidence

ORD record
ord-091b58f2c6fa4f128773609d6684683f
Source dataset
uspto-grants-2015_02
Patent number
US08962657B2

Reaction notes

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