Sodium Carbonate → (RS)-4-(3'-difluoromethoxy-biphenyl-3-yl)-4-(4-difluoromethoxy-3-methyl-phenyl)-4,5-dihydro-oxazol-2-ylamine

HRID 1668770Notes

Reaction equation

HRID 1668770 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:8]2([C:14]3[CH:19]=[CH:18][C:17]([O:20][CH:21]([F:23])[F:22])=[C:16]([CH3:24])[CH:15]=3)[CH2:12][O:11][C:10]([NH2:13])=[N:9]2)[CH:5]=[CH:6][CH:7]=1.[F:25][CH:26]([F:37])[O:27][C:28]1[CH:29]=[C:30](B(O)O)[CH:31]=[CH:32][CH:33]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Na+].[Na+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.COCCOC>[F:25][CH:26]([F:37])[O:27][C:28]1[CH:33]=[C:32]([C:2]2[CH:7]=[CH:6][CH:5]=[C:4]([C:8]3([C:14]4[CH:19]=[CH:18][C:17]([O:20][CH:21]([F:22])[F:23])=[C:16]([CH3:24])[CH:15]=4)[CH2:12][O:11][C:10]([NH2:13])=[N:9]3)[CH:3]=2)[CH:31]=[CH:30][CH:29]=1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 177500693-(Difluoromethoxy)benzeneboronic acidHCID 57825083(RS)-4-(3-Bromo-phenyl)-4-(4-difluoromethoxy-3-methyl-phenyl)-4,5-dihydro-oxazol-2-ylamine

Product 1

HCID 57825198(RS)-4-(3'-difluoromethoxy-biphenyl-3-yl)-4-(4-difluoromethoxy-3-methyl-phenyl)-4,5-dihydro-oxazol-2-ylamineYield 31.1%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
100 °C

Procedure

A dried pressure tube was charged with (RS)-4-(3-bromo-phenyl)-4-(4-difluoromethoxy-3-methyl-phenyl)-4,5-dihydro-oxazol-2-ylamine (Building Block S) (131 mg, 0.3 mmol), 3-(difluoromethoxy)-benzeneboronic acid (93 mg, 0.5 mmol), triphenylphosphine (18 mg, 0.1 mmol), 2 N sodium carbonate solution (0.5 mL), and 1,2-dimethoxyethane (3 mL). The mixture was purged with nitrogen before palladium(II) acetate (7 mg, 0.03 mmol) was added. The sealed pressure tube was heated at 100° C. for 15 hours. For the working-up, the reaction mixture was cooled and evaporated under reduced pressure. The residue was directly chromatographed on silica gel using a gradient of dichloromethane/methanol=100/0 to 95/5 as the eluent. There were obtained 43 mg (28% of theory) of (RS)-4-(3′-difluoromethoxy-biphenyl-3-yl)-4-(4-difluoromethoxy-3-methyl-phenyl)-4,5-dihydro-oxazol-2-ylamine as light yellow solid. Mass (calculated) C24H20F4N2O3 [460]; (found) [M+H]+=461.

Workup

  1. additionwas added
  2. temperaturethe reaction mixture was cooled
  3. customevaporated under reduced pressure
  4. customThe residue was directly chromatographed on silica gel using a gradient of dichloromethane/methanol=100/0 to 95/5 as the eluent

Sources & evidence

ORD record
ord-1d430ea6ef7f463991f019c354cc21fd
Source dataset
uspto-grants-2011_08
Patent number
US07989449B2

Reaction notes

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