Water → [1-(1-Trifluoromethyl-cyclopropylmethyl)-piperidin-4-yl]-methanol

HRID 222593Notes

Reaction equation

HRID 222593 reaction equation
C([O:3][C:4]([CH:6]1[CH2:11][CH2:10][N:9]([C:12]([C:14]2([C:17]([F:20])([F:19])[F:18])[CH2:16][CH2:15]2)=O)[CH2:8][CH2:7]1)=O)C.[H-].[Al+3].[Li+].[H-].[H-].[H-].O.[OH-].[Na+].O>O1CCCC1>[F:19][C:17]([F:18])([F:20])[C:14]1([CH2:12][N:9]2[CH2:8][CH2:7][CH:6]([CH2:4][OH:3])[CH2:11][CH2:10]2)[CH2:15][CH2:16]1

Participants

6

Reactant 4

HCID 962WaterHCID 21226445Aluminium lithium hydrideHCID 23719242Sodium hydroxide--water (1/1/1)HCID 668652731-(1-Trifluoromethyl-cyclopropanecarbonyl)-piperidine-4-carboxylic acid ethyl ester

Product 1

HCID 66865643[1-(1-Trifluoromethyl-cyclopropylmethyl)-piperidin-4-yl]-methanolYield 42%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

1-(1-Trifluoromethyl-cyclopropanecarbonyl)-piperidine-4-carboxylic acid ethyl ester (50 g; 170.48 mmol) in tetrahydrofuran (350 mL) is added to a solution of 1 M lithium aluminum hydride (170.48 mL; 170.48 mmol) in tetrahydrofuran. The reaction mixture is allowed to warm to room temperature and stirred for 1 h. The reaction mixture is cooled at 0° C. and water/2 M aqueous solution of sodium hydroxide/water (1:3:1) are added sequentially (8.5 mL:12 mL:8.5 mL). The resulting slurry is filtered over a celite® pad and washed with tetrahydrofuran (200 mL). The organic layer is concentrated under controlled vacuum to afford 17 g of the volatile title compound as colorless oil. The crude material is used without further purification. MS (m/z) 238 (M+1).

Workup

  1. temperatureThe reaction mixture is cooled at 0° C.
  2. filtrationThe resulting slurry is filtered over a celite® pad
  3. washwashed with tetrahydrofuran (200 mL)
  4. concentrationThe organic layer is concentrated under controlled vacuum

Sources & evidence

ORD record
ord-cf1395a0a0fa4cce9a67158a6e797cb2
Source dataset
uspto-grants-2012_06
Patent number
US08207344B2

Reaction notes

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