Hydrochloric Acid → HCID 58016787, compound

HRID 1926978Notes

Reaction equation

HRID 1926978 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][CH:21]([CH3:26])[CH2:22][CH:23]([OH:25])[CH3:24])=[N:17][CH:16]=[N:15][C:14]=3[O:13][C:12]=2[C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)=[CH:7][CH:6]=1.Br[CH2:34][C:35]([O:37]C(C)(C)C)=[O:36].Cl>C1(C)C=CC=CC=1.S([O-])(O)(=O)=O.C([N+](CCCC)(CCCC)CCCC)CCC>[CH3:3][O:4][C:5]1[CH:6]=[CH:7][C:8]([C:11]2[C:19]3[C:18]([O:20][CH:21]([CH3:26])[CH2:22][CH:23]([CH3:24])[O:25][CH2:34][C:35]([OH:37])=[O:36])=[N:17][CH:16]=[N:15][C:14]=3[O:13][C:12]=2[C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)=[CH:9][CH:10]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 79177tert-Butyl bromoacetateHCID 58016930HCID 58016930, compound

Product 1

HCID 58016787HCID 58016787, compound

Reagents, catalysts & solvents 2

HCID 94433Tetrabutylammonium hydrogen sulfateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
70 °C

Procedure

Add 4.8 ml of 11.25 N sodium hydroxide solution to a solution of 2.19 g (5.41 mmol) 4-{[5-(4-methoxyphenyl)-6-phenylfuro[2,3-d]pyrimidin-4-yl]oxy}pentan-2-ol in 20 ml toluene. After adding 184 mg (0.54 mmol) tetra-n-butylammonium hydrogensulphate and 2.11 g (10.83 mmol) tert.-butyl bromoacetate, stir the reaction mixture for 15 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, and filter. Concentrate the filtrate by vacuum evaporation. Take up the residue in ethyl acetate and purify by flash chromatography on silica gel (solvent: first ethyl acetate, then ethyl acetate/methanol 5:1). Purify the product obtained once more by preparative RP-HPLC (gradient: water/acetonitrile). 0.29 g (11% of theor.) of the desired product is obtained as a racemic mixture of diastereomers.

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 the filtrate
  7. customby vacuum evaporation
  8. custompurify by flash chromatography on silica gel (solvent
  9. customPurify the product
  10. customobtained once more by preparative RP-HPLC (gradient: water/acetonitrile)

Sources & evidence

ORD record
ord-6879d0da75cc43d5a5fa17c924c77400
Source dataset
uspto-grants-2012_05
Patent number
US08183246B2

Reaction notes

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