4-Cyanopiperidine → HCID 67772408, compound

HRID 1808840Notes

Reaction equation

HRID 1808840 reaction equation
[NH:1]1[CH2:6][CH2:5][CH:4]([C:7]#[N:8])[CH2:3][CH2:2]1.[F:9][C:10]1[CH:25]=[CH:24][C:13]([C:14]([N:16]([CH3:23])[C@@H:17]([CH:20]([CH3:22])[CH3:21])[CH:18]=O)=[O:15])=[CH:12][C:11]=1[CH3:26].[Na].[BH4-].[Na+]>CCO.C(Cl)Cl>[C:7]([CH:4]1[CH2:5][CH2:6][N:1]([CH2:18][C@@H:17]([N:16]([CH3:23])[C:14](=[O:15])[C:13]2[CH:24]=[CH:25][C:10]([F:9])=[C:11]([CH3:26])[CH:12]=2)[CH:20]([CH3:21])[CH3:22])[CH2:2][CH2:3]1)#[N:8]

Participants

7

Reactant 4

HCID 1382234-CyanopiperidineHCID 4311764Sodium borohydrideHCID 5360545SodiumHCID 86666002HCID 86666002, compound

Product 1

HCID 67772408HCID 67772408, compoundYield 4%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6344DichloromethaneSolvent

Procedure

TEA (0.552 mL, 3.98 mmol) was added to a mixture of piperidine-4-carbonitrile (0.132 g, 1.19 mmol) in EtOH (2 mL) and DCM (3 mL). To the mixture was added (S)-4-fluoro-N,3-dimethyl-N-(3-methyl-1-oxobutan-2-yl)benzamide (Compound A2.1) (0.2 g, 0.80 mmol). The resultant mixture was stirred at rt for 15 min before sodium triacetoxyhydroborate (0.337 g, 1.59 mmol) was added. The stirring was continued at rt over night. Sodium tetrahydroborate (0.015 g, 0.40 mmol) was added and the mixture was stirred for 1 h. The solvents were removed on a vacuum centrifuge. The residue was diluted with DCM and washed with NaOH (aq., 1M). The organic phase was filtered through a phase separator and concentrated under reduced pressure. The residue was purified by preparative HPLC. The product containing fractions was concentrated and the residue was purified a second time by preparative HPLC using Chiralpak IC 5 μm 20×250 mm column and Heptan/EtOH/TEA 60/40/0.1, as mobile phase to give the title compound (11 mg, 4%). Enantiomeric excess: 98.2%. Mixture of rotamers: (400 MHz, CD3OD) δ 0.85-1.08, 1.69-2.02, 2.12-2.96, 3.37-3.50, 4.41-4.59, 7.07-7.16, 7.19-7.36.

Workup

  1. additionwas added
  2. waitThe stirring was continued at rt over night
  3. customThe solvents were removed on a vacuum centrifuge
  4. additionThe residue was diluted with DCM
  5. washwashed with NaOH (aq., 1M)
  6. filtrationThe organic phase was filtered through a phase separator
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by preparative HPLC
  9. additionThe product containing fractions
  10. concentrationwas concentrated
  11. customthe residue was purified a second time by preparative HPLC

Sources & evidence

ORD record
ord-ce1788b8e5bf495ca38a07af3222dbf2
Source dataset
uspto-grants-2013_01
Patent number
US08361998B2

Reaction notes

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