Formaldehyde → 1-methylpiperidin-4-yl (2R)-2-((1R)-3,3-difluorocyclopentyl)-2-hydroxy-2-phenylethanoate

HRID 458729Notes

Reaction equation

HRID 458729 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.C=O.[C:27]([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]([CH3:27])[CH2:15][CH2:16]2)=[O:9])[CH2:3]1

Participants

7

Reactant 3

HCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 69766623piperidin-4-yl(2R)-((1R)-3,3-difluorocyclopentyl)-2-hydroxy-2-phenylethanoate

Product 1

HCID 697685131-methylpiperidin-4-yl (2R)-2-((1R)-3,3-difluorocyclopentyl)-2-hydroxy-2-phenylethanoate

Reagents, catalysts & solvents 3

HCID 3007855ZincchlorideCatalystHCID 887MethanolSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 17 mg of piperidin-4-yl (2R)-((1R)-3,3-difluorocyclopentyl)-2-hydroxy-2-phenylethanoate and 0.03 ml of formaldehyde (35% aqueous solution) in 1 ml of methanol, 0.3 ml of advancedly prepared 0.3 M methanol solution of sodium cyanoborohydride and zinc chloride (1:0.5) was added at room temperature, followed by 30 minutes' stirring at the same temperature. The reaction liquid was diluted with ethyl acetate, washed successively with a saturated sodium hydrogencarbonate solution and with saturated brine, and dried over anhydrous sodium sulfate. Distilling the solvent off under reduced pressure, 19 mg of the title compound was obtained.

Workup

  1. customThe reaction liquid
  2. washwashed successively with a saturated sodium hydrogencarbonate solution and with saturated brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. distillationDistilling the solvent off under reduced pressure

Sources & evidence

ORD record
ord-70e51a9b99254726beb041e4ed9cd3f4
Source dataset
uspto-grants-2007_03
Patent number
US07192969B2

Reaction notes

Loading…