Water → (S)-tert-butyl 2-((S)-1-cyano-2-(4'-cyano-3'-fluorobiphenyl-4-yl)ethylcarbamoyl)piperidine-1-carboxylate

HRID 600298Notes

Reaction equation

HRID 600298 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][CH2:10][C@H:9]1[C:14]([OH:16])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH2:17][C@H:18]([C:35]#[N:36])[CH2:19][C:20]1[CH:25]=[CH:24][C:23]([C:26]2[CH:31]=[CH:30][C:29]([C:32]#[N:33])=[C:28]([F:34])[CH:27]=2)=[CH:22][CH:21]=1.C(N(CC)CC)C.O>CN(C=O)C.[Cl-].[Na+].O>[C:35]([C@@H:18]([NH:17][C:14]([C@@H:9]1[CH2:10][CH2:11][CH2:12][CH2:13][N:8]1[C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])=[O:16])[CH2:19][C:20]1[CH:25]=[CH:24][C:23]([C:26]2[CH:31]=[CH:30][C:29]([C:32]#[N:33])=[C:28]([F:34])[CH:27]=2)=[CH:22][CH:21]=1)#[N:36]

Participants

7

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 688617(2S)-1-((tert-butoxy)carbonyl)piperidine-2-carboxylic acidHCID 57999676(S)-4'-(2-Amino-2-cyanoethyl)-3-fluorobiphenyl-4-carbonitrile

Product 1

HCID 57999649(S)-tert-butyl 2-((S)-1-cyano-2-(4'-cyano-3'-fluorobiphenyl-4-yl)ethylcarbamoyl)piperidine-1-carboxylateYield 73.6%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 57417360Sodium chloride; waterSolvent

Procedure

A 50% solution of propane phosphonic acid anhydride (0.964 g) (T3P) in DMF was added to a stirred solution of (S)-1-(tert-butoxycarbonyl)piperidine-2-carboxylic acid (0.290 g), (S)-4′-(2-amino-2-cyanoethyl)-3-fluorobiphenyl-4-carbonitrile (0.335 g) and triethylamine (0.880 mL) in DMF (3 mL) at 0° C. The resulting solution was allowed to warm to RT and stirred for 18 h. The mixture was poured into water and brine and the mixture extracted with ethyl acetate. The organics were washed with saturated brine, dried and evaporated. The crude product was purified by flash silica chromatography, eluting with 30% ethyl acetate in isohexane. Pure fractions were evaporated to dryness to afford (S)-tert-butyl 2-((S)-1-cyano-2-(4′-cyano-3′-fluorobiphenyl-4-yl)ethylcarbamoyl)piperidine-1-carboxylate as a colourless solid (0.443 g).

Workup

  1. extractionthe mixture extracted with ethyl acetate
  2. washThe organics were washed with saturated brine
  3. customdried
  4. customevaporated
  5. customThe crude product was purified by flash silica chromatography
  6. washeluting with 30% ethyl acetate in isohexane
  7. customPure fractions were evaporated to dryness

Sources & evidence

ORD record
ord-fa1947d68126405cad8f6bd65245b396
Source dataset
uspto-grants-2011_03
Patent number
US07902181B2

Reaction notes

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