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

HRID 538317Notes

Reaction equation

HRID 538317 reaction equation
[NH2:1][C:2]([C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([Br:20])[N:15]=1)([CH3:13])[CH2:3][O:4][C@@:5]([CH3:12])([C:8]([F:11])([F:10])[F:9])[C:6]#[N:7].C(N[C@H](C(O)=O)CS)(=O)C.C([O-])([O-])=O.[K+].[K+]>CCO>[Br:20][C:16]1[N:15]=[C:14]([C:2]2([CH3:13])[CH2:3][O:4][C@@:5]([CH3:12])([C:8]([F:10])([F:9])[F:11])[C:6]([NH2:7])=[N:1]2)[CH:19]=[CH:18][CH:17]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 12035N-Acetyl-L-CysteineHCID 86668027(R)-2-[(RS)-2-amino-2-(6-bromo-pyridin-2-yl)-propoxy]-3,3,3-trifluoro-2-methyl-propionitrile

Product 1

HCID 86668026(R)-5-(6-Bromo-pyridin-2-yl)-2,5-dimethyl-2-trifluoromethyl-5,6-dihydro-2H-[1,4]oxazin-3-ylamine

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A suspension of (R)-2-[(RS)-2-amino-2-(6-bromo-pyridin-2-yl)-propoxy]-3,3,3-trifluoro-2-methyl-propionitrile (0.688 g, 1.172 mmol), N-acetyl-L-cysteine (0.383 g, 2.344 mmol) and K2CO3 (0.356 g, 2.560 mmol) in abs. EtOH (4 ml) was stirred at 80° C. for 18 h. The reaction mixture was quenched with 10% aq. K2CO3 soln. and 3× extracted with TBME. The combined org. phases were washed with brine, dried over Na2SO4, filtered and concentrated to leave the title compound as a colourless solid. HPLC RtH4=0.68-0.70 min; ESIMS: 352, 354 [(M+H)].

Workup

  1. customThe reaction mixture was quenched with 10% aq. K2CO3 soln
  2. extractionand 3× extracted with TBME
  3. washphases were washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-6e1122c31bf14a21a19f625212459dfe
Source dataset
uspto-grants-2014_10
Patent number
US08865712B2

Reaction notes

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