3-Hydroxybenzaldehyde → 3-((4,4-Difluorocyclohexyl)methoxy)benzaldehyde

HRID 882494Notes

Reaction equation

HRID 882494 reaction equation
CS([O:5][CH2:6][CH:7]1[CH2:12][CH2:11][C:10]([F:14])([F:13])[CH2:9][CH2:8]1)(=O)=O.O[C:16]1[CH:17]=[C:18]([CH:21]=[CH:22][CH:23]=1)[CH:19]=[O:20].C([O-])([O-])=O.[K+].[K+].CN1C(=O)CCC1>O>[F:13][C:10]1([F:14])[CH2:11][CH2:12][CH:7]([CH2:6][O:5][C:16]2[CH:17]=[C:18]([CH:21]=[CH:22][CH:23]=2)[CH:19]=[O:20])[CH2:8][CH2:9]1

Participants

6

Reactant 4

HCID 1013-HydroxybenzaldehydeHCID 11430Potassium CarbonateHCID 13387N-methyl-2-pyrrolidoneHCID 10868050(4,4-Difluorocyclohexyl)methyl methanesulfonate

Product 1

HCID 580277013-((4,4-Difluorocyclohexyl)methoxy)benzaldehyde

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Mesylate 142 (0.9 g, 3.94 mmole), 3-hydroxybenzaldehyde (0.577 g, 4.73 mmole), K2CO3 (0.817 g, 5.91 mmole) and NMP (5 ml) were heated at 70° C. overnight. H2O (30 ml) and hexanes (50 ml) was added and stirred for 1 hr. The organic layer was dried over Na2SO4 and evaporated. Purification by flash chromatography (20% ether/hexanes gradient) gave 3-((4,4-difluorocyclohexyl)methoxy)benzaldehyde (143) as an oil. Yield (0.559 g, 56%): 1H NMR (400 MHz, DMSO-d6) δ 9.95 (s, 1H), 7.51-7.46 (m, 2H), 7.41-7.40 (m, 1H), 7.25 (dt, J=6.8, 2.8 Hz, 1H), 3.91 (d, J=6.0 Hz, 2H), 2.06-1.98 (m, 5H), 1.89-1.73 (m, 5H), 1.37-1.27 (m, 2H).

Workup

  1. dry with materialThe organic layer was dried over Na2SO4
  2. customevaporated
  3. customPurification by flash chromatography (20% ether/hexanes gradient)

Sources & evidence

ORD record
ord-c5e2d4f76ac2404e8ad8ed9532042ed9
Source dataset
uspto-grants-2015_03
Patent number
US08993807B2

Reaction notes

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