Sodium Carbonate → HCID 56961221, compound

HRID 1851650Notes

Reaction equation

HRID 1851650 reaction equation
CS([O:5][C@@:6]([C:16]1[CH:21]=[C:20]([F:22])[CH:19]=[CH:18][C:17]=1[NH2:23])([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:26]([O-])([O-])=[O:27].[Na+].[Na+].ClC(Cl)(OC(=O)OC(Cl)(Cl)Cl)Cl.[H][H]>>[CH:13]1([C:12]#[C:11][C@:6]2([C:7]([F:10])([F:9])[F:8])[C:16]3[CH:21]=[C:20]([F:22])[CH:19]=[CH:18][C:17]=3[NH:23][C:26](=[O:27])[O:5]2)[CH2:15][CH2:14]1

Participants

6

Reactant 5

HCID 10340Sodium Carbonate2×HCID 14798Sodium HydroxideHCID 94429TriphosgeneHCID 87279954HCID 87279954, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 56961221HCID 56961221, compound

Conditions

Temperature
15 °C

Procedure

(R)-2-(2-Amino-5-fluorophenyl)-4-cyclopropyl-1,1,1-trifluorobut-3-yn-2-ol methanesulfonate (CN46619-MSA) of example 4 (14.0 g, 33.5 mmol) in ethyl acetate/heptanes (40 g, 6/4 v/v) was charged to a jacketed 150 mL-reactor with agitator and off-gas scrubber with caustic soda. After addition of aqueous Na2CO3 (12%-w/w, 26.9 g, 30.3 mmol) the mixture was stirred for 5 min at 15° C. The aqueous phase was separated and discarded. Aqueous Na2CO3 (12%-w/w, 34.1 g, 38.4 mmol) was charged to the organic phase, then triphosgene (3.73 g, 12.6 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 charged with heptanes (15.9 g), the phases were separated and the aqueous phase discarded. The organic phase was washed with water (12 mL), dried over MgSO4, filtered and concentrated to dryness. After drying under vacuum at 50° C., the product (R)-4-(cyclopropylethynyl)-6-fluoro-4-(trifluoromethyl)-1,4-dihydro-2H-3,1-benzoxazin-2-one (CN46686, compound of formula I, wherein R1 is trifluoromethyl, R2 is cyclopropyl, R8 is 6-fluoro, R9 is hydrogen and R1° is hydrogen 9.78 g, 32.7 mmol, 97%) was obtained as a yellowish solid (99.4% 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 to dryness
  8. customAfter drying under vacuum at 50° C.
  9. customwas obtained as a yellowish solid (99.4% purity, according to Method C)

Sources & evidence

ORD record
ord-2eda6b9f9849440cab63d36e9a59ebe1
Source dataset
uspto-grants-2015_02
Patent number
US08957204B2

Reaction notes

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