Trifluoroacetic acid → methyl (2R)-2-amino-5-[5-[{2-[3,5-bis(trifluoromethyl)phenyl]-2-methylpropanoyl}(methyl)amino]-4-(4-fluoro-2-methylphenyl)-2-pyridinyl]-4-pentynoate

HRID 69537Notes

Reaction equation

HRID 69537 reaction equation
FC(F)(F)C(O)=O.[F:8][C:9]([F:58])([F:57])[C:10]1[CH:11]=[C:12]([C:20]([CH3:56])([CH3:55])[C:21]([N:23]([CH3:54])[C:24]2[C:25]([C:46]3[CH:51]=[CH:50][C:49]([F:52])=[CH:48][C:47]=3[CH3:53])=[CH:26][C:27]([C:30]#[C:31][CH2:32][C@@H:33]([NH:38]C(OC(C)(C)C)=O)[C:34]([O:36][CH3:37])=[O:35])=[N:28][CH:29]=2)=[O:22])[CH:13]=[C:14]([C:16]([F:19])([F:18])[F:17])[CH:15]=1>ClCCl.C([O-])(O)=O.[Na+]>[NH2:38][C@H:33]([CH2:32][C:31]#[C:30][C:27]1[CH:26]=[C:25]([C:46]2[CH:51]=[CH:50][C:49]([F:52])=[CH:48][C:47]=2[CH3:53])[C:24]([N:23]([C:21](=[O:22])[C:20]([C:12]2[CH:11]=[C:10]([C:9]([F:57])([F:58])[F:8])[CH:15]=[C:14]([C:16]([F:18])([F:17])[F:19])[CH:13]=2)([CH3:55])[CH3:56])[CH3:54])=[CH:29][N:28]=1)[C:34]([O:36][CH3:37])=[O:35]

Participants

5

Reactant 2

HCID 6422Trifluoroacetic acidHCID 57965578HCID 57965578, compound2×

Product 1

HCID 57965568methyl (2R)-2-amino-5-[5-[{2-[3,5-bis(trifluoromethyl)phenyl]-2-methylpropanoyl}(methyl)amino]-4-(4-fluoro-2-methylphenyl)-2-pyridinyl]-4-pentynoateYield 89.5%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 516892Sodium BicarbonateSolvent

Procedure

Trifluoroacetic acid (15 ml) was added dropwise to an ice-cooled solution of methyl (2R)-5-[5-[{2-[3,5-bis(trifluoromethyl)phenyl]-2-methylpropanoyl}(methyl)amino]-4-(4-fluoro-2-methylphenyl)-2-pyridinyl]-2-({[(1,1-dimethylethyl)oxy]carbonyl}amino)-4-pentynoate (Intermediate 12, 2.4 g, 3.32 mmol) in anhydrous Dichloromethane (45 ml) and the resulting reaction mixture was stirred at room temperature for 1 h. Volatiles were evaporated. The reaction crude was taken-up in saturated NaHCO3 aqueous solution [until pH=7] (30 ml) and extracted with DCM (2×50 ml). The organic layers were collected, dried over sodium sulphate, filtered and evaporated to obtain the title compound (1.85 g, 2.97 mmol, 89% yield) as a brown solid. UPLC: Rt 0.78 min, m/z 624 [M+H+].

Workup

  1. customthe resulting reaction mixture
  2. customVolatiles were evaporated
  3. customThe reaction crude
  4. extractionextracted with DCM (2×50 ml)
  5. customThe organic layers were collected
  6. dry with materialdried over sodium sulphate
  7. filtrationfiltered
  8. customevaporated

Sources & evidence

ORD record
ord-d31fa97d712f4ae6853666d41317c1d4
Source dataset
uspto-grants-2014_09
Patent number
US08822504B2

Reaction notes

Loading…