Methanol → 4-(4-Fluorophenyl)-3-hydroxymethylpiperidine-6-one

HRID 2296771Notes

Reaction equation

HRID 2296771 reaction equation
CC(C[AlH]CC(C)C)C.C(C[CH2:14][CH:15]1[CH:20]([C:21]2[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=2)[CH2:19][C:18](=[O:28])[NH:17][CH2:16]1)(O)=O.C[OH:30]>O1CCCC1.C1(C)C=CC=CC=1>[F:27][C:24]1[CH:25]=[CH:26][C:21]([CH:20]2[CH2:19][C:18](=[O:28])[NH:17][CH2:16][CH:15]2[CH2:14][OH:30])=[CH:22][CH:23]=1

Participants

6

Reactant 3

HCID 887MethanolHCID 14487Diisobutylaluminum hydrideHCID 227338414-(4-Fluorophenyl)-3-carboxyethylpiperidin-6-one

Product 1

HCID 227338464-(4-Fluorophenyl)-3-hydroxymethylpiperidine-6-oneYield 67%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
23 °C

Procedure

DIBAL-H (15.1 ml, 0.0225 mol) was added at a rate of 50 ml/hour, by means of a syringe pump, to a solution of 3-carboxyethyl-4-(4-fluorophenyl)-piperidine-6-one (1.99 g, 0.0075 mol) in tetrahydrofuran (15 ml) at −70° C. under an argon atmosphere keeping the temperature below 0° C. The mixture was allowed to warm to 23° C. and stirred for 45 minutes, then a solution of methanol (0.9 ml) in toluene (7.5 ml) was added to destroy the excess DIBAL-H, followed by 30% potassium carbonate solution (8.5 ml), all below 30° C. The organic phase was separated, dried with anhydrous sodium sulphate, filtered, and evaporated to afford the title compound (1.54 g) as a slightly colored oil, which was crystallized by trituration with ether. Yield 67%.

Workup

  1. customat −70° C.
  2. customthe temperature below 0° C
  3. customto destroy the excess DIBAL-H
  4. customfollowed by 30% potassium carbonate solution (8.5 ml), all below 30° C
  5. customThe organic phase was separated
  6. dry with materialdried with anhydrous sodium sulphate
  7. filtrationfiltered
  8. customevaporated

Sources & evidence

ORD record
ord-bfd08db5136f4e3b8406173eca8ca5f9
Source dataset
uspto-grants-2002_12
Patent number
US06489347B1

Reaction notes

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