Sodium Carbonate → HCID 67127447, compound

HRID 870299Notes

Reaction equation

HRID 870299 reaction equation
CS([O:5][C@@:6]([C:16]1[CH:17]=[C:18]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH:19]=[CH:20][C:21]=1[NH2:22])([C:11]#[C:12][CH:13]1[CH2:15][CH2:14]1)[C:7]([F:10])([F:9])[F:8])(=O)=O.[OH-].[Na+].[C:31]([O-])([O-])=[O:32].[Na+].[Na+].ClC(Cl)(OC(=O)OC(Cl)(Cl)Cl)Cl>C(OCC)(=O)C>[CH:13]1([C:12]#[C:11][C@:6]2([C:7]([F:10])([F:9])[F:8])[C:16]3[CH:17]=[C:18]([C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)[CH:19]=[CH:20][C:21]=3[NH:22][C:31](=[O:32])[O:5]2)[CH2:15][CH2:14]1

Participants

6

Reactant 4

HCID 10340Sodium Carbonate2×HCID 14798Sodium HydroxideHCID 94429TriphosgeneHCID 87279909HCID 87279909, compound

Product 1

HCID 67127447HCID 67127447, compoundYield 98%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
15 °C

Procedure

(R)-2-(4-Aminobiphenyl-3-yl)-4-cyclopropyl-1,1,1-trifluorobut-3-yn-2-ol methanesulfonate (CN46630-MSA) of example 2 (14.7 g, 34.4 mmol) in ethyl acetate/heptanes (1:1 v/v, 27.9 g) was charged in a jacketed 150 mL-reactor with agitator and off-gas scrubber with caustic soda. After addition of aqueous Na2CO3 (12%-w/w, 32.3 g, 36.4 mmol, formation of gas during addition!) the mixture was stirred for 15 min at 15° C. The aqueous phase was separated and discarded. Aqueous Na2CO3 (12%-w/w, 41 g, 46 mol) and ethyl acetate (20 g) were charged to the organic phase. Triphosgene (4.41 g, 14.9 mmol) was added in portions over a period of 25 min at 10° C. The reaction mixture was stirred for 2 h at 8° C. The mixture was diluted with ethyl acetate (45 g) and the phases were separated. The aqueous phase was discarded. The organic phase was washed with water (12 mL), dried over MgSO4, filtered and concentrated and dried at 50° C. under reduced pressure to obtain (R)-4-(cyclopropylethynyl)-6-phenyl-4-(trifluoromethyl)-1,4-dihydro-2H-3,1-benzoxazin-2-one (CN46685, 12.1 g, 33.9 mmol, 98%) as a yellowish solid (99.5% purity, according to Method C).

Workup

  1. customThe aqueous phase was separated
  2. stirringThe reaction mixture was stirred for 2 h at 8° C
  3. customthe phases were separated
  4. washThe organic phase was washed with water (12 mL)
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customdried at 50° C. under reduced pressure

Sources & evidence

ORD record
ord-e23947bead5343f0aab288fc9598c28d
Source dataset
uspto-grants-2015_03
Patent number
US08969550B2

Reaction notes

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