Hydrochloric Acid → [2-({[5-(4-Ethylphenyl)-6-phenylfuro[2,3-d]pyrimidin-4-yl]oxy}methyl)-3,3-dimethylbutoxy]-acetic acid tert.-butyl ester

HRID 1926946Notes

Reaction equation

HRID 1926946 reaction equation
[OH-].[Na+].[CH2:3]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[C:19]3[C:18]([O:20][CH2:21][CH:22]([C:25]([CH3:28])([CH3:27])[CH3:26])[CH2:23][OH:24])=[N:17][CH:16]=[N:15][C:14]=3[O:13][C:12]=2[C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)=[CH:7][CH:6]=1)[CH3:4].[C:35]([O:39][C:40](=[O:43])[CH2:41]Br)([CH3:38])([CH3:37])[CH3:36].Cl>C1(C)C=CC=CC=1.S([O-])(O)(=O)=O.C([N+](CCCC)(CCCC)CCCC)CCC>[C:35]([O:39][C:40](=[O:43])[CH2:41][O:24][CH2:23][CH:22]([CH2:21][O:20][C:18]1[C:19]2[C:11]([C:8]3[CH:7]=[CH:6][C:5]([CH2:3][CH3:4])=[CH:10][CH:9]=3)=[C:12]([C:29]3[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=3)[O:13][C:14]=2[N:15]=[CH:16][N:17]=1)[C:25]([CH3:28])([CH3:27])[CH3:26])([CH3:38])([CH3:37])[CH3:36]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 79177tert-Butyl bromoacetateHCID 580168362-({[5-(4-Ethylphenyl)-6-phenylfuro[2,3-d]pyrimidin-4-yl]oxy}methyl)-3,3-dimethylbutan-1-ol

Product 1

HCID 58016779[2-({[5-(4-Ethylphenyl)-6-phenylfuro[2,3-d]pyrimidin-4-yl]oxy}methyl)-3,3-dimethylbutoxy]-acetic acid tert.-butyl ester

Reagents, catalysts & solvents 2

HCID 94433Tetrabutylammonium hydrogen sulfateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
70 °C

Procedure

Add 0.5 ml of 11.25 N sodium hydroxide solution to a solution of 265 mg (0.62 mmol) 2-({[5-(4-ethylphenyl)-6-phenylfuro[2,3-d]pyrimidin-4-yl]oxy}methyl)-3,3-dimethylbutan-1-ol in 10 ml toluene. After adding 21 mg (0.06 mmol) tetra-n-butylammonium hydrogensulphate and 240 mg (1.23 mmol) 2-bromoacetic acid tert.-butyl ester, stir the reaction mixture for 16 h at 70° C. After cooling to room temperature, neutralize with 1 N hydrochloric acid and extract with ethyl acetate. Wash the organic phase with satd. aqueous sodium chloride solution, dry over sodium sulphate, and filter. Concentrate the filtrate by vacuum evaporation. Purify the residue by preparative RP-HPLC (gradient: water/acetonitrile). 170 mg (51% of theor.) of the desired product (racemate) is obtained.

Workup

  1. temperatureAfter cooling to room temperature
  2. extractionextract with ethyl acetate
  3. washWash the organic phase with satd
  4. dry with materialaqueous sodium chloride solution, dry over sodium sulphate
  5. filtrationfilter
  6. concentrationConcentrate the filtrate
  7. customby vacuum evaporation
  8. customPurify the residue by preparative RP-HPLC (gradient: water/acetonitrile)

Sources & evidence

ORD record
ord-281514177254418296658c5e5966b362
Source dataset
uspto-grants-2012_05
Patent number
US08183246B2

Reaction notes

Loading…