Potassium Carbonate → (2R,5R)-5-(6-bromo-3-fluoro-pyridin-2-yl)-2,5-dimethyl-2-trifluoromethyl-5,6-dihydro-2H-[1,4]oxazin-3-ylamine

HRID 538370Notes

Reaction equation

HRID 538370 reaction equation
[Br:1][C:2]1[N:7]=[C:6]([C@:8]([NH:20]S(C2C=CC([N+]([O-])=O)=CC=2)(=O)=O)([CH3:19])[CH2:9][O:10][C@@:11]([C:17]#[N:18])([CH3:16])[C:12]([F:15])([F:14])[F:13])[C:5]([F:33])=[CH:4][CH:3]=1.C(N[C@H](C(O)=O)CS)(=O)C.C([O-])([O-])=O.[K+].[K+]>C(O)C>[Br:1][C:2]1[N:7]=[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)[C:5]([F:33])=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 12035N-Acetyl-L-CysteineHCID 86668078N-[(R)-1-(6-bromo-3-fluoro-pyridin-2-yl)-2-((R)-1-cyano-2,2,2-trifluoro-1-methyl-ethoxy)-1-methyl-ethyl]-4-nitro-benzenesulfonamide

Product 1

HCID 86668039(2R,5R)-5-(6-bromo-3-fluoro-pyridin-2-yl)-2,5-dimethyl-2-trifluoromethyl-5,6-dihydro-2H-[1,4]oxazin-3-ylamineYield 74.4%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
80 °C

Procedure

A solution of N—[(R)-1-(6-bromo-3-fluoro-pyridin-2-yl)-2-((R)-1-cyano-2,2,2-trifluoro-1-methyl-ethoxy)-1-methyl-ethyl]-4-nitro-benzenesulfonamide (9.18 g, 16.53 mmol) and N-acetylcysteine (5.40 g, 33.10 mmol) in 92 ml ethanol was evacuated and flushed with nitrogen. K2CO3 (4.57 g, 33.1 mmol) was added and the mixture was stirred at 80° C. for 3 days. The reaction mixture was concentrated in vacuo to about ¼ of the original volume and partitioned between water and TBME. The organic layer was washed with 10% aq. K2CO3 solution, dried over Na2SO4, filtered and evaporated to give a yellow oil. Column chromatography on silica (hexanes/14-50% (EtOAc:MeOH 95:5)) gave 4.55 g of the title compound as an off-white solid.

Workup

  1. customflushed with nitrogen
  2. concentrationThe reaction mixture was concentrated in vacuo to about ¼ of the original volume
  3. custompartitioned between water and TBME
  4. washThe organic layer was washed with 10% aq. K2CO3 solution
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. customevaporated
  8. customto give a yellow oil

Sources & evidence

ORD record
ord-6f663924281f4932a276a42985263629
Source dataset
uspto-grants-2014_10
Patent number
US08865712B2

Reaction notes

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