Hydrochloric Acid → 2-({[5-(4-Ethylphenyl)-6-phenylfuro[2,3-d]pyrimidin-4-yl]oxy}methyl)-3,3-dimethylbutan-1-ol

HRID 1926912Notes

Reaction equation

HRID 1926912 reaction equation
[OH-].[Na+].[C:3]([CH:7]([CH2:10][OH:11])[CH2:8][OH:9])([CH3:6])([CH3:5])[CH3:4].Cl[C:13]1[C:14]2[C:21]([C:22]3[CH:27]=[CH:26][C:25]([CH2:28][CH3:29])=[CH:24][CH:23]=3)=[C:20]([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)[O:19][C:15]=2[N:16]=[CH:17][N:18]=1.Cl>C1(C)C=CC=CC=1.COCCOC.O.S([O-])(O)(=O)=O.C([N+](CCCC)(CCCC)CCCC)CCC>[CH2:28]([C:25]1[CH:24]=[CH:23][C:22]([C:21]2[C:14]3[C:13]([O:9][CH2:8][CH:7]([C:3]([CH3:6])([CH3:5])[CH3:4])[CH2:10][OH:11])=[N:18][CH:17]=[N:16][C:15]=3[O:19][C:20]=2[C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)=[CH:27][CH:26]=1)[CH3:29]

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 1002262-Tert-butylpropane-1,3-diolHCID 580168974-Chloro-5-(4-ethylphenyl)-6-phenylfuro[2,3-d]pyrimidine

Product 1

HCID 580168362-({[5-(4-Ethylphenyl)-6-phenylfuro[2,3-d]pyrimidin-4-yl]oxy}methyl)-3,3-dimethylbutan-1-ol

Reagents, catalysts & solvents 4

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

Conditions

Temperature
70 °C

Procedure

Add 2.7 ml of 11.25 N sodium hydroxide solution to a solution of 1974 mg (14.93 mmol) 2-tert.-butylpropane-1,3-diol in 25 ml toluene, 8 ml 1,2-dimethoxyethane and 8 ml water at 70° C. After adding 101 mg (0.30 mmol) tetra-n-butylammonium hydrogensulphate and 1000 mg (2.99 mmol) 4-chloro-5-(4-ethylphenyl)-6-phenylfuro[2,3-d]pyrimidine, stir the reaction mixture for 17 h at 70° C. After cooling to room temperature, adjust to pH 7 with concentrated hydrochloric acid. Extract with dichloromethane. Wash the organic phase with satd. sodium chloride solution, dry over sodium sulphate, and filter. Concentrate the filtrate by vacuum evaporation. Mix the residue with methanol, filter, and wash with diethyl ether. Purify the filtrate by preparative RP-HPLC (gradient: water/acetonitrile). 275 mg (21% of theor.) of the desired product (racemate) is obtained.

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 the filtrate
  7. customby vacuum evaporation
  8. additionMix the residue with methanol
  9. filtrationfilter
  10. washwash with diethyl ether
  11. customPurify the filtrate by preparative RP-HPLC (gradient: water/acetonitrile)

Sources & evidence

ORD record
ord-ee14d551e0b74745823d189abe2e32c5
Source dataset
uspto-grants-2012_05
Patent number
US08183246B2

Reaction notes

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