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 2196287Notes

Reaction equation

HRID 2196287 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

5

Reactant 3

HCID 11430Potassium CarbonateHCID 12035N-Acetyl-L-CysteineHCID 66665422N-[(R)-1-(5-bromo-2-fluoro-phenyl)-2-((R)-1-cyano-2,2,2-trifluoro-1-methyl-ethoxy)-1-methyl-ethyl]-2-nitro-benzenesulfonamide

Product 1

HCID 66666066rel-(2R,5R)-5-(5-Bromo-2-fluorophenyl)-2,5-dimethyl-2-(trifluoromethyl)-5,6-dihydro-2H-1,4-oxazin-3-amine

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

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

  1. customAfter removal of the solvent the residue
  2. dissolutionwas dissolved in water
  3. extractionextracted with EtOAc
  4. washCombined extracts were washed with saturated NaHCO3 solution and brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-13a7d4f6039a4a6ebb872bec8ff3c38c
Source dataset
uspto-grants-2012_12
Patent number
US08338413B1

Reaction notes

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