Ethyl Acetate → 4-{1-[2,5-Difluoro-4-(1-hydroxy-ethyl)-phenyl]-piperidin-4-ylideneaminooxy}-piperidine-1-carboxylic acid isopropyl ester

HRID 2066861Notes

Reaction equation

HRID 2066861 reaction equation
[BH4-].[Na+].[CH:3]([O:6][C:7]([N:9]1[CH2:14][CH2:13][CH:12]([O:15][N:16]=[C:17]2[CH2:22][CH2:21][N:20]([C:23]3[CH:28]=[C:27]([F:29])[C:26]([C:30](=[O:32])[CH3:31])=[CH:25][C:24]=3[F:33])[CH2:19][CH2:18]2)[CH2:11][CH2:10]1)=[O:8])([CH3:5])[CH3:4].C(OCC)(=O)C>CO.C([O-])(O)=O.[Na+]>[CH:3]([O:6][C:7]([N:9]1[CH2:14][CH2:13][CH:12]([O:15][N:16]=[C:17]2[CH2:18][CH2:19][N:20]([C:23]3[CH:28]=[C:27]([F:29])[C:26]([CH:30]([OH:32])[CH3:31])=[CH:25][C:24]=3[F:33])[CH2:21][CH2:22]2)[CH2:11][CH2:10]1)=[O:8])([CH3:5])[CH3:4]

Participants

6

Reactant 3

HCID 8857Ethyl AcetateHCID 4311764Sodium borohydrideHCID 866550104-[1-(4-Acetyl-2,5-difluoro-phenyl)-piperidin-4-ylideneaminooxy]-piperidine-1-carboxylic acid isopropyl ester

Product 1

HCID 583335224-{1-[2,5-Difluoro-4-(1-hydroxy-ethyl)-phenyl]-piperidin-4-ylideneaminooxy}-piperidine-1-carboxylic acid isopropyl ester

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 516892Sodium BicarbonateSolvent

Procedure

NaBH4 (0.15 g, 3.9 mmol) was added at 0° C. to a stirred solution of 50a (0.15 g, 0.34 mmol) in 5 mL of methanol. After 1 h, the mixture was diluted with 10 mL of saturated NaHCO3 and stirred for 20 minutes. The mixture was poured into ethyl acetate (25 mL), washed twice with brine (25 mL), dried and concentrated under vacuum. The residue was purified on an AS-H column (elution with 5% EtOH+0.1% triethylamine in hexane) to afford the 2 enantiomers of 4-{1-[2,5-difluoro-4-(1-hydroxy-ethyl)-phenyl]-piperidin-4-ylideneaminooxy}-piperidine-1-carboxylic acid isopropyl ester 50-1, LC-MS 422.2 (MFE-18), tR=6.45 (Method 2). EC50: 48 nM. 78 mg of the first enantiomer and 46 mg of the second enantiomer were obtained.

Workup

  1. washwashed twice with brine (25 mL)
  2. customdried
  3. concentrationconcentrated under vacuum
  4. customThe residue was purified on an AS-H column (elution with 5% EtOH+0.1% triethylamine in hexane)

Sources & evidence

ORD record
ord-37e9fc74101c4b4899f526f39dd16d0c
Source dataset
uspto-grants-2012_10
Patent number
US08293729B2

Reaction notes

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