Hydrochloric Acid → HCID 58016826, compound

HRID 1926964Notes

Reaction equation

HRID 1926964 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][CH:22]([CH3:25])[CH2:23][OH:24])=[N:17][CH:16]=[N:15][C:14]=3[O:13][C:12]=2[C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)=[CH:7][CH:6]=1.Br[CH2:33][C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35].Cl>C1(C)C=CC=CC=1.S([O-])(O)(=O)=O.C([N+](CCCC)(CCCC)CCCC)CCC>[C:37]([O:36][C:34](=[O:35])[CH2:33][O:24][CH2:23][CH:22]([CH3:25])[CH2:21][O:20][C:18]1[C:19]2[C:11]([C:8]3[CH:7]=[CH:6][C:5]([O:4][CH3:3])=[CH:10][CH:9]=3)=[C:12]([C:26]3[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=3)[O:13][C:14]=2[N:15]=[CH:16][N:17]=1)([CH3:40])([CH3:39])[CH3:38]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 79177tert-Butyl bromoacetateHCID 58016956HCID 58016956, compound

Product 1

HCID 58016826HCID 58016826, compound

Reagents, catalysts & solvents 2

HCID 94433Tetrabutylammonium hydrogen sulfateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
70 °C

Procedure

Add 1.14 ml of 12.5 N sodium hydroxide solution to a solution of 500 mg (1.28 mmol) 3-{[5-(4-methoxyphenyl)-6-phenylfuro[2,3-d]pyrimidin-4-yl]oxy}-2-methylpropan-1-ol in 10 ml toluene at 70° C. After adding 44 mg (0.13 mmol) tetra-n-butylammonium hydrogensulphate and 500 mg (2.56 mmol) tert.-butyl bromoacetate, stir the reaction mixture for 20 h at 70° C. After cooling to room temperature, adjust to pH 7 with concentrated hydrochloric acid and extract three times with 50 ml dichloromethane each time. Wash the combined organic extracts with satd. aqueous sodium chloride solution, dry over sodium sulphate, filter, and concentrate by vacuum evaporation. Purify the raw product by preparative RP-HPLC (gradient: water/acetonitrile). 298 mg (46% of theor.) of the desired product is obtained as racemate.

Workup

  1. temperatureAfter cooling to room temperature
  2. extractionextract three times with 50 ml dichloromethane each time
  3. washWash the combined organic extracts with satd
  4. dry with materialaqueous sodium chloride solution, dry over sodium sulphate
  5. filtrationfilter
  6. concentrationconcentrate by vacuum evaporation
  7. customPurify the raw product by preparative RP-HPLC (gradient: water/acetonitrile)

Sources & evidence

ORD record
ord-5a6061ea18a849369137c35460655125
Source dataset
uspto-grants-2012_05
Patent number
US08183246B2

Reaction notes

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