Potassium Carbonate → rel-(2R,5R)-5-(5-Bromo-2-fluorophenyl)-2,5-dimethyl-2-(trifluoromethyl)-5,6-dihydro-2H-1,4-oxazin-3-amine

HRID 39237

Reaction equation

[Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:33])=[C:6]([C@:8]([NH:20]S(C2C=CC=CC=2[N+]([O-])=O)(=O)=O)([CH3:19])[CH2:9][O:10][C@@:11]([C:17]#[N:18])([CH3:16])[C:12]([F:15])([F:14])[F:13])[CH:7]=1.C(N[C@H](C(O)=O)CS)(=O)C.C([O-])([O-])=O.[K+].[K+]>CO>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:33])=[C:6]([C@:8]2([CH3:19])[CH2:9][O:10][C@@:11]([CH3:16])([C:12]([F:15])([F:14])[F:13])[C:17]([NH2:18])=[N:20]2)[CH:7]=1

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of N—[(R)-1-(5-bromo-2-fluoro-phenyl)-2-((R)-1-cyano-2,2,2-trifluoro-1-methyl-ethoxy)-1-methyl-ethyl]-2-nitro-benzenesulfonamide (6.54 g, 11.8 mmol) and N-acetyl-cysteine (2.4 g, 26.0 mmol) in MeOH (80 ml) was added K2CO3 (3.62 g, 26.0 mmol) and the reaction mixture was heated at 80° C. for 16 h. After removal of the solvent the residue was dissolved in water and extracted with EtOAc. Combined extracts were washed with saturated NaHCO3 solution and brine, dried over MgSO4, filtered and concentrated to provide the title compound after chromatographic purification over silica gel (hexane-EtOAc 10:1 to 1:2 containing 0.03% NEt3) as a yellow oil: TLC (hexane-EtOAc 1:1): Rf=0.58; UPLC RtH5=0.843 min; ESIMS: 369, 371 [(M+H)+]; 1H NMR (360 MHz, CDCl3): δ 7.66 (dd, 1H), 7.35 (m, 1H), 6.91 (dd, 1H), 3.97 (m, 2H), 1.53 (s, 3H), 1.49 (s, 3H).

Workup

customAfter removal of the solvent the residue
dissolutionwas dissolved in water
extractionextracted with EtOAc
washCombined extracts were washed with saturated NaHCO3 solution and brine
dry with materialdried over MgSO4
filtrationfiltered
concentrationconcentrated

Sources & evidence

ORD record: ord-2cef23638b254d129cd9b02c2b2162de
Source dataset: uspto-grants-2013_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08524897B2

Linked notes

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