2-Bromo-1-(4,5-dihydro-5-(2,6-difluorophenyl)-3-isoxazolyl)ethanone → ethyl 5-[4-[5-(2,6-difluorophenyl)-4,5-dihydro-3-isoxazolyl]-2-thiazolyl]tetrahydro-2H-1,2-oxazine-2-carboxylate

HRID 75181Notes

Reaction equation

HRID 75181 reaction equation
[NH2:1][C:2](=[S:14])[CH:3]1[CH2:8][O:7][N:6]([C:9]([O:11][CH2:12][CH3:13])=[O:10])[CH2:5][CH2:4]1.Br[CH2:16][C:17]([C:19]1[CH2:23][CH:22]([C:24]2[C:29]([F:30])=[CH:28][CH:27]=[CH:26][C:25]=2[F:31])[O:21][N:20]=1)=O>CO>[F:31][C:25]1[CH:26]=[CH:27][CH:28]=[C:29]([F:30])[C:24]=1[CH:22]1[O:21][N:20]=[C:19]([C:17]2[N:1]=[C:2]([CH:3]3[CH2:8][O:7][N:6]([C:9]([O:11][CH2:12][CH3:13])=[O:10])[CH2:5][CH2:4]3)[S:14][CH:16]=2)[CH2:23]1

Participants

4

Reactant 2

HCID 866575632-Bromo-1-(4,5-dihydro-5-(2,6-difluorophenyl)-3-isoxazolyl)ethanone2×HCID 86674475HCID 86674475, compound2×

Product 1

HCID 67322192ethyl 5-[4-[5-(2,6-difluorophenyl)-4,5-dihydro-3-isoxazolyl]-2-thiazolyl]tetrahydro-2H-1,2-oxazine-2-carboxylate

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of ethyl 5-(aminothioxomethyl)tetrahydro-2H-1,2-oxazine-2-carboxylate (i.e. the product of Step I) (0.19 g, 0.87 mmol) and 2-bromo-1-(4,5-dihydro-5-(2,6-difluorophenyl)-3-isoxazolyl)ethanone (the product of Example 1, Step C) (0.264 g, 0.87 mmol) in methanol (2 mL) was heated at 50° C. for 1 h. Methanol was removed under reduced pressure and the resulting material was partitioned between sodium acetate (10%, 5 mL) and diethyl ether (5 mL). The layers were separated and the aqueous phase was extracted with diethyl ether (2×). The organic fractions were concentrated under reduced pressure to provide the title compound as a pale-tan oil (0.383 g).

Workup

  1. customMethanol was removed under reduced pressure
  2. customthe resulting material was partitioned between sodium acetate (10%, 5 mL) and diethyl ether (5 mL)
  3. customThe layers were separated
  4. extractionthe aqueous phase was extracted with diethyl ether (2×)
  5. concentrationThe organic fractions were concentrated under reduced pressure

Sources & evidence

ORD record
ord-8b7ec090eb3d49edb14d78c5f3f6a0f4
Source dataset
uspto-grants-2014_09
Patent number
US08835427B2

Reaction notes

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