Hydrochloric Acid → {[1-({[5-(4-Methoxyphenyl)-6-phenylfuro[2,3-d]pyrimidin-4-yl]oxy}methyl)cyclobutyl]methoxy}-acetic acid tert-butyl ester

HRID 2189126Notes

Reaction equation

HRID 2189126 reaction equation
[OH-].[Na+].[CH3:3][O:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]2[C:19]3[C:18]([O:20][CH2:21][C:22]4([CH2:26][OH:27])[CH2:25][CH2:24][CH2:23]4)=[N:17][CH:16]=[N:15][C:14]=3[O:13][C:12]=2[C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)=[CH:7][CH:6]=1.[C:34]([O:38][C:39](=[O:42])[CH2:40]Br)([CH3:37])([CH3:36])[CH3:35].Cl>C1(C)C=CC=CC=1.S([O-])(O)(=O)=O.C([N+](CCCC)(CCCC)CCCC)CCC>[C:34]([O:38][C:39](=[O:42])[CH2:40][O:27][CH2:26][C:22]1([CH2:21][O:20][C:18]2[C:19]3[C:11]([C:8]4[CH:7]=[CH:6][C:5]([O:4][CH3:3])=[CH:10][CH:9]=4)=[C:12]([C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=4)[O:13][C:14]=3[N:15]=[CH:16][N:17]=2)[CH2:25][CH2:24][CH2:23]1)([CH3:37])([CH3:36])[CH3:35]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 79177tert-Butyl bromoacetateHCID 58280249[1-({[5-(4-Methoxyphenyl)-6-phenylfuro[2,3-d]pyrimidin-4-yl]oxy}methyl)cyclobutyl]methanol

Product 1

HCID 58280083{[1-({[5-(4-Methoxyphenyl)-6-phenylfuro[2,3-d]pyrimidin-4-yl]oxy}methyl)cyclobutyl]methoxy}-acetic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 94433Tetrabutylammonium hydrogen sulfateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
70 °C

Procedure

Add 0.6 ml of an 11.25N sodium hydroxide solution to a solution of 285 mg (0.68 mmol) of [1-({[5-(4-methoxyphenyl)-6-phenylfuro[2,3-d]pyrimidin-4-yl]oxy}methyl)cyclobutyl]methanol in 5 ml of toluene. After adding 23 mg (0.07 mmol) of tetra-n-butylammonium hydrogensulphate and 267 mg (1.37 mmol) of bromoacetic acid tert-butyl ester, stir the reaction mixture at 70° C. for20 h. After cooling to room temperature, adjust to pH 7 with conc. hydrochloric acid. Extract three times with 20 ml each time of dichloromethane. Wash the combined organic extracts with satd. aqueous sodium chloride solution, dry over sodium sulphate and filter. Concentrate the filtrate under reduced pressure. Purify the crude product by means of preparative RP-HPLC (gradient: water/acetonitrile). 260 mg (72% of theory) of the desired product are obtained.

Workup

  1. temperatureAfter cooling to room temperature
  2. extractionExtract three times with 20 ml each time of dichloromethane
  3. washWash the combined organic extracts with satd
  4. dry with materialaqueous sodium chloride solution, dry over sodium sulphate
  5. filtrationfilter
  6. concentrationConcentrate the filtrate under reduced pressure
  7. customPurify the crude product by means of preparative RP-HPLC (gradient: water/acetonitrile)

Sources & evidence

ORD record
ord-c1ffa93de33d4c26b8485cbed92869bd
Source dataset
uspto-grants-2012_12
Patent number
US08324222B2

Reaction notes

Loading…