Formylcycloheptane → 1-(cycloheptyl-methyl)piperidin-4-yl (2R)-((1R)-3,3-difluorocyclopentyl)-2-hydroxy-2-phenylethanoate

HRID 1761158Notes

Reaction equation

HRID 1761158 reaction equation
[F:1][C:2]1([F:24])[CH2:6][CH2:5][C@@H:4]([C@@:7]([OH:23])([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C:8]([O:10][CH:11]2[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]2)=[O:9])[CH2:3]1.[CH:25]1([CH:32]=O)[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]1.C([BH3-])#N.[Na+]>CO.C(OCC)(=O)C.[Cl-].[Zn+2].[Cl-]>[F:24][C:2]1([F:1])[CH2:6][CH2:5][C@@H:4]([C@@:7]([OH:23])([C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)[C:8]([O:10][CH:11]2[CH2:12][CH2:13][N:14]([CH2:32][CH:25]3[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]3)[CH2:15][CH2:16]2)=[O:9])[CH2:3]1

Participants

7

Reactant 3

HCID 77961FormylcycloheptaneHCID 5003444Sodium cyanoborohydrideHCID 69766623piperidin-4-yl(2R)-((1R)-3,3-difluorocyclopentyl)-2-hydroxy-2-phenylethanoate

Product 1

HCID 865973021-(cycloheptyl-methyl)piperidin-4-yl (2R)-((1R)-3,3-difluorocyclopentyl)-2-hydroxy-2-phenylethanoate

Reagents, catalysts & solvents 3

HCID 3007855ZincchlorideCatalystHCID 887MethanolSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 9.3 mg of piperidin-4-yl(2R)-((1R)-3,3-difluorocyclopentyl)-2-hydroxy-2-phenylethanoate in 1 ml of methanol, 10 mg of cycloheptanecarbaldehyde and then 0.5 ml of advancedly prepared 0.3 M methanol solution of sodium cyanoborohydride and zinc chloride (1:0.5) were added at room temperature, followed by 30 minutes' stirring at the same temperature. The reaction liquid was diluted with ethyl acetate, washed successively with saturated sodium hydrogenecarbonate solution and with saturated brine, and dried over anhydrous sodium sulfate. Distilling the solvent off under reduced pressure, the residue was purified on preparative thin layer chromatography (Kieselgel™60F254, Art5744 (Merck), chloroform/methanol=10/1) to provide the title compound.

Workup

  1. customThe reaction liquid
  2. washwashed successively with saturated sodium hydrogenecarbonate solution and with saturated brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. distillationDistilling the solvent off under reduced pressure
  5. customthe residue was purified on preparative thin layer chromatography (Kieselgel™60F254, Art5744 (Merck), chloroform/methanol=10/1)

Sources & evidence

ORD record
ord-c6350c2a9a224820a763bd6f4fe1f8e2
Source dataset
uspto-grants-2005_01
Patent number
US06846835B2

Reaction notes

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