Triethylamine → (R)-[4-(4-Cyanobenzoylamino)-1-(3,3,3-trifluoro-2-hydroxy-2-methylpropionyl)piperidine]

HRID 1814805Notes

Reaction equation

HRID 1814805 reaction equation
[NH2:1][CH:2]1[CH2:7][CH2:6][N:5]([C:8](=[O:16])[C@:9]([OH:15])([CH3:14])[C:10]([F:13])([F:12])[F:11])[CH2:4][CH2:3]1.C(N(CC)CC)C.[C:24]([C:26]1[CH:34]=[CH:33][C:29]([C:30](Cl)=[O:31])=[CH:28][CH:27]=1)#[N:25]>CCOC(C)=O>[C:24]([C:26]1[CH:34]=[CH:33][C:29]([C:30]([NH:1][CH:2]2[CH2:7][CH2:6][N:5]([C:8](=[O:16])[C@:9]([OH:15])([CH3:14])[C:10]([F:12])([F:13])[F:11])[CH2:4][CH2:3]2)=[O:31])=[CH:28][CH:27]=1)#[N:25]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 801724-Cyanobenzoyl chlorideHCID 20773310(R)-[4-amino-1-(3,3,3-trifluoro-2-hydroxy-2-methylpropionyl)piperidine]

Product 1

HCID 20773309(R)-[4-(4-Cyanobenzoylamino)-1-(3,3,3-trifluoro-2-hydroxy-2-methylpropionyl)piperidine]Yield 36.6%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent2×

Procedure

To a solution of (R)-[4-amino-1-(3,3,3-trifluoro-2-hydroxy-2-methylpropionyl)piperidine] (Example 21, 170 mg, 0.71 mmol) and triethylamine (0.12 mg, 0.86 mmol) in EtOAc (15 ml) was added a solution of 4-cyanobenzoylchloride (130 mg, 0.78 mmol) in EtOAc (10 ml). The resultant mixture was stirred at ambient temperature for 4 hours, washed with 1 M hydrochloric acid, saturated sodium hydrogen carbonate solution and brine, dried and evaporated. The residue was chromatographed on silica with 50% EtOAc/DCM as eluent to give the title compound as a solid (97 mg, 0.26 mmol). NMR: 1.45 (m, 2H), 1.65 (s, 3H), 2.1 (m, 2H), 3.05 (m, 2H), 4.2 (m, 1H), 4.4-4.6 (m, 2H), 5.1 (s, 1H), 6.2 (d, 1H), 7.65 (d, 2H), 7.8 (d, 2H); m/z 368.

Workup

  1. washwashed with 1 M hydrochloric acid, saturated sodium hydrogen carbonate solution and brine
  2. customdried
  3. customevaporated
  4. customThe residue was chromatographed on silica with 50% EtOAc/DCM as eluent

Sources & evidence

ORD record
ord-715e2b84d2e441a195297d3f93439db9
Source dataset
uspto-grants-2005_04
Patent number
US06878712B1

Reaction notes

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