Hydrochloric Acid → 3-{[5-(4-Ethylphenyl)-6-(2-fluorophenyl)furo[2,3-d]pyrimidin-4-yl]oxy}cyclohexanol

HRID 2189075Notes

Reaction equation

HRID 2189075 reaction equation
[OH-].[Na+].[CH:3]1([OH:10])[CH2:8][CH2:7][CH2:6][CH:5]([OH:9])[CH2:4]1.Cl[C:12]1[C:13]2[C:20]([C:21]3[CH:26]=[CH:25][C:24]([CH2:27][CH3:28])=[CH:23][CH:22]=3)=[C:19]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=3[F:35])[O:18][C:14]=2[N:15]=[CH:16][N:17]=1.Cl>C1(C)C=CC=CC=1.COCCOC.O.S([O-])(O)(=O)=O.C([N+](CCCC)(CCCC)CCCC)CCC>[CH2:27]([C:24]1[CH:23]=[CH:22][C:21]([C:20]2[C:13]3[C:12]([O:9][CH:5]4[CH2:6][CH2:7][CH2:8][CH:3]([OH:10])[CH2:4]4)=[N:17][CH:16]=[N:15][C:14]=3[O:18][C:19]=2[C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=2[F:35])=[CH:26][CH:25]=1)[CH3:28]

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 104331,3-CyclohexanediolHCID 14798Sodium HydroxideHCID 580167964-Chloro-5-(4-ethylphenyl)-6-(2-fluorophenyl)furo[2,3-d]pyrimidine

Product 1

HCID 582801733-{[5-(4-Ethylphenyl)-6-(2-fluorophenyl)furo[2,3-d]pyrimidin-4-yl]oxy}cyclohexanol

Reagents, catalysts & solvents 4

HCID 94433Tetrabutylammonium hydrogen sulfateCatalystHCID 962WaterSolventHCID 1140TolueneSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
70 °C

Procedure

Add 4.5 ml of 12.5N sodium hydroxide solution at 70° C. to a mixture of 1.65 g (14.17 mmol) of cyclohexane-1,3-diol in 45 ml of toluene, 15 ml of 1,2-dimethoxyethane and 15 ml of water. After adding 0.19 g (0.57 mmol) of tetra-n-butylammonium hydrogen sulfate and 2.0 g (5.67 mmol) of 4-chloro-5-(4-ethylphenyl)-6-(2-fluorophenyl)furo[2,3-d]pyrimidine, stir the reaction mixture at 70° C. for 17 hours. After cooling to room temperature, adjust to pH 7 with conc. hydrochloric acid. Extract with dichloromethane. Wash the organic phase with satd. sodium chloride solution, dry over sodium sulphate, filter and concentrate under reduced pressure. Chromatograph the residue on silica gel (eluent: cyclohexane/ethyl acetate 2:1). 0.60 g (24% of theory) of the desired product are obtained as a racemic diastereomer mixture.

Workup

  1. temperatureAfter cooling to room temperature
  2. extractionExtract with dichloromethane
  3. washWash the organic phase with satd
  4. dry with materialsodium chloride solution, dry over sodium sulphate
  5. filtrationfilter
  6. concentrationconcentrate under reduced pressure

Sources & evidence

ORD record
ord-7c8b9096c4724d0595e609e846a2ddc5
Source dataset
uspto-grants-2012_12
Patent number
US08324222B2

Reaction notes

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