Trifluoroacetic acid → 5-Cyano-pyridine-2-carboxylic acid [3-((R)-5-amino-3-difluoromethyl-3,6-dihydro-2H-[1,4]oxazin-3-yl)-4-fluoro-phenyl]-amide

HRID 221788Notes

Reaction equation

HRID 221788 reaction equation
C(OC(=O)[NH:7][C:8]1[CH2:9][O:10][CH2:11][C@:12]([C:17]2[CH:22]=[C:21]([NH:23][C:24]([C:26]3[CH:31]=[CH:30][C:29]([C:32]#[N:33])=[CH:28][N:27]=3)=[O:25])[CH:20]=[CH:19][C:18]=2[F:34])([CH:14]([F:16])[F:15])[N:13]=1)(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH2:7][C:8]1[CH2:9][O:10][CH2:11][C@:12]([C:17]2[CH:22]=[C:21]([NH:23][C:24]([C:26]3[CH:31]=[CH:30][C:29]([C:32]#[N:33])=[CH:28][N:27]=3)=[O:25])[CH:20]=[CH:19][C:18]=2[F:34])([CH:14]([F:16])[F:15])[N:13]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 66665639((R)-5-{5-[(5-Cyano-pyridine-2-carbonyl)-amino]-2-fluoro-phenyl}-5-difluoromethyl-5,6-dihydro-2H-[1,4]oxazin-3-yl)-carbamic acid tert-butyl ester

Product 1

HCID 581188885-Cyano-pyridine-2-carboxylic acid [3-((R)-5-amino-3-difluoromethyl-3,6-dihydro-2H-[1,4]oxazin-3-yl)-4-fluoro-phenyl]-amide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

((R)-5-{5-[(5-Cyano-pyridine-2-carbonyl)-amino]-2-fluoro-phenyl}-5-difluoromethyl-5,6-dihydro-2H-[1,4]oxazin-3-yl)-carbamic acid tert-butyl ester (44.47 g, 91.0 mmol) was dissolved in 450 ml DCM and mildly chilled with a rt water bath. TFA (150 ml) was added. The reaction was slightly exothermic. The mixture was stirred for 1.5 h at rt. The volatiles were removed with vacuum at rt. The residue was taken up in DCM and the procedure repeated twice. The residue was taken up in 3 L EtOAc and washed with 10% aqueous Na2CO3 and brine. The organic phase was dried with sodium sulfate and partially evaporated. iPrOH was added and the mixture chilled. The title compound was collected as snow-white crystals. Yield 30.56 g.

Workup

  1. customThe volatiles were removed with vacuum at rt
  2. washwashed with 10% aqueous Na2CO3 and brine
  3. dry with materialThe organic phase was dried with sodium sulfate
  4. custompartially evaporated
  5. additioniPrOH was added
  6. temperaturethe mixture chilled
  7. customThe title compound was collected as snow-white crystals

Sources & evidence

ORD record
ord-42a435257f114ef893d688cb7e4e9c65
Source dataset
uspto-grants-2012_06
Patent number
US08207164B2

Reaction notes

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