4-Fluorobenzyl chloride → HCID 19848749, compound

HRID 1608174Notes

Reaction equation

HRID 1608174 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][OH:15])[CH2:10][CH2:9]1)=O)(C)(C)C.[H-].[Na+].[F:18][C:19]1[CH:26]=[CH:25][C:22]([CH2:23][Cl:24])=[CH:21][CH:20]=1>CN(C)C=O.[I-].C([N+](CCCC)(CCCC)CCCC)CCC>[ClH:24].[F:18][C:19]1[CH:26]=[CH:25][C:22]([CH2:23][O:15][CH2:14][CH:11]2[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]2)=[CH:21][CH:20]=1

Participants

6

Reactant 3

HCID 96024-Fluorobenzyl chlorideHCID 24758Sodium hydrideHCID 2764081Tert-butyl 4-(hydroxymethyl)piperidine-1-carboxylate

Product 1

HCID 19848749HCID 19848749, compoundYield 84.6%

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 6228DimethylformamideSolvent

Procedure

To a solution of 5.0 g (23.2 mmole) of the 4-hydroxymethyl-piperidine-1-carboxylic acid t-butyl ester produced above, in 100 ml of dimethylformamide, was added 1.2 g (25.6 mmole) of a 50% sodium hydride oil dispersion. After stirring for 0.5 hours, 5.0 g (34.9 mmole) of 4-fluorobenzyl chloride was added, followed by a catalytic amount of tetrabutylammonium iodide. The suspension was stirred an additional 24 hours, quenched with saturated aqueous sodium chloride and extracted with ether. The organic layer was dried with magnesium sulfate and concentrated. The resulting oil was treated with methanolic hydrogen chloride for 4 hours. A white solid was obtained upon concentration, which was filtered and washed with hexane. 5.1 g of 4-(4-fluoro-benzyloxymethyl)-piperidine hydrochloride was obtained which had a melting point of 142°-145° C.

Workup

  1. stirringThe suspension was stirred an additional 24 hours
  2. customquenched with saturated aqueous sodium chloride
  3. extractionextracted with ether
  4. dry with materialThe organic layer was dried with magnesium sulfate
  5. concentrationconcentrated
  6. additionThe resulting oil was treated with methanolic hydrogen chloride for 4 hours
  7. customA white solid was obtained upon concentration, which
  8. filtrationwas filtered
  9. washwashed with hexane

Sources & evidence

ORD record
ord-658987ff172b4794a8aad826ba255afc
Source dataset
uspto-grants-1989_09
Patent number
US04870083

Reaction notes

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