1-Bromopentane → 4-(4-Ethoxy-2,3-difluorophenyl)-1-pentylcyclohexanol

HRID 1016228Notes

Reaction equation

HRID 1016228 reaction equation
Br[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6].[Mg].[CH2:8]([O:10][C:11]1[CH:16]=[CH:15][C:14]([CH:17]2[CH2:22][CH2:21][C:20](=[O:23])[CH2:19][CH2:18]2)=[C:13]([F:24])[C:12]=1[F:25])[CH3:9].C(OC1C=CC=C(F)C=1F)C.C([Li])CCC.O1C2(CCC(=O)CC2)OCC1>C1COCC1>[CH2:8]([O:10][C:11]1[CH:16]=[CH:15][C:14]([CH:17]2[CH2:18][CH2:19][C:20]([CH2:2][CH2:3][CH2:4][CH2:5][CH3:6])([OH:23])[CH2:21][CH2:22]2)=[C:13]([F:24])[C:12]=1[F:25])[CH3:9]

Participants

8

Reactant 6

HCID 80571-BromopentaneHCID 5674151,4-Dioxaspiro[4.5]decan-8-oneHCID 27829281-Ethoxy-2,3-DifluorobenzeneHCID 5462224MagnesiumHCID 111611214-(4-Ethoxy-2,3-difluorophenyl)cyclohexanoneHCID 178418339Butyllithium

Product 1

HCID 113248664-(4-Ethoxy-2,3-difluorophenyl)-1-pentylcyclohexanol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 54.5 ml of 1-bromopentane in 200 ml of THF was added dropwise to 10.7 g of magnesium turnings under a layer of 100 ml of THF, and the mixture was subsequently refluxed for 1 hour. A solution of 104.5 g of 4-(4-ethoxy-2,3-difluorophenyl)cyclohexanone (obtainable by lithiation of 4-ethoxy-2,3-difluorobenzene using n-butyllithium, reaction with 1,4-dioxaspiro[4.5]decan-8-one, dehydration and hydrogenation of the resultant alkene, followed by removal of the carbonyl protecting group under acidic conditions) in 500 ml of THF was then added dropwise at 40° C., and the mixture was refluxed for 2 hours. Conventional work-up gave 4-(4-ethoxy-2,3-difluorophenyl)-1-pentylcyclohexanol.

Workup

  1. temperaturethe mixture was subsequently refluxed for 1 hour
  2. customfollowed by removal of the carbonyl protecting group under acidic conditions) in 500 ml of THF
  3. additionwas then added dropwise at 40° C.
  4. temperaturethe mixture was refluxed for 2 hours

Sources & evidence

ORD record
ord-4c64d663bf7d4d409adf7adfdfad1139
Source dataset
uspto-grants-2002_11
Patent number
US06475595B1

Reaction notes

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