Water → (6R)-6-{[6-(2-Fluorophenyl)-5-(4-methoxyphenyl)furo[2,3-d]pyrimidin-4-yl]oxy}heptanoic acid tert.-butyl ester

HRID 1926941Notes

Reaction equation

HRID 1926941 reaction equation
[H-].[Na+].[C:3]([O:7][C:8](=[O:16])[CH2:9][CH2:10][CH2:11][CH2:12][C@H:13]([OH:15])[CH3:14])([CH3:6])([CH3:5])[CH3:4].Cl[C:18]1[C:19]2[C:26]([C:27]3[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[CH:29][CH:28]=3)=[C:25]([C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=3[F:41])[O:24][C:20]=2[N:21]=[CH:22][N:23]=1.O>C1COCC1.[I-].C([N+](CCCC)(CCCC)CCCC)CCC.C(OCC)(=O)C>[C:3]([O:7][C:8](=[O:16])[CH2:9][CH2:10][CH2:11][CH2:12][C@H:13]([O:15][C:18]1[C:19]2[C:26]([C:27]3[CH:28]=[CH:29][C:30]([O:33][CH3:34])=[CH:31][CH:32]=3)=[C:25]([C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=3[F:41])[O:24][C:20]=2[N:21]=[CH:22][N:23]=1)[CH3:14])([CH3:4])([CH3:6])[CH3:5]

Participants

8

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 580168704-Chloro-6-(2-fluorophenyl)-5-(4-methoxyphenyl)furo[2,3-d]pyrimidineHCID 58016950tert-butyl (6R)-6-hydroxyheptanoate

Product 1

HCID 25096414(6R)-6-{[6-(2-Fluorophenyl)-5-(4-methoxyphenyl)furo[2,3-d]pyrimidin-4-yl]oxy}heptanoic acid tert.-butyl ester

Reagents, catalysts & solvents 3

HCID 67553Tetrabutylammonium IodideCatalystHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

Add 87 mg (2.16 mmol) sodium hydride (60% dispersion in mineral oil) to a solution of 350 mg (1.73 mmol) (6R)-6-hydroxyheptanoic acid tert.-butyl ester in 5 ml THF, with ice cooling. After stirring for ten minutes with ice cooling, add a solution of 644 mg (1.82 mmol) 4-chloro-6-(2-fluorophenyl)-5-(4-methoxyphenyl)furo[2,3-d]pyrimidine in 5 ml THF and 32 mg (0.09 mmol) tetra-n-butylammonium iodide. Stir the reaction mixture for 48 h at RT. After adding water and ethyl acetate, wash the separated organic phase with 1 N hydrochloric acid and concentrate by vacuum evaporation. Take up the residue in acetonitrile/DMSO and purify by preparative RP-HPLC (gradient: water/acetonitrile). 425 mg (47% of theor.) of the desired product is obtained.

Workup

  1. stirringStir the reaction mixture for 48 h at RT
  2. washwash the separated organic phase with 1 N hydrochloric acid
  3. concentrationconcentrate by vacuum evaporation
  4. custompurify by preparative RP-HPLC (gradient: water/acetonitrile)

Sources & evidence

ORD record
ord-fb284f12a8a84906bef647b3b198bb32
Source dataset
uspto-grants-2012_05
Patent number
US08183246B2

Reaction notes

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