Water → 4-{[(3R)-1-Benzylpiperidin-3-yl]oxy}-6-(2-fluorophenyl)-5-(4-methoxyphenyl)furo[2,3-d]pyrimidine

HRID 2189076Notes

Reaction equation

HRID 2189076 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][CH2:11][C@@H:10]([OH:14])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].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>[CH2:1]([N:8]1[CH2:13][CH2:12][CH2:11][C@@H:10]([O:14][C:18]2[C:19]3[C:26]([C:27]4[CH:28]=[CH:29][C:30]([O:33][CH3:34])=[CH:31][CH:32]=4)=[C:25]([C:35]4[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=4[F:41])[O:24][C:20]=3[N:21]=[CH:22][N:23]=2)[CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

8

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 693761(R)-1-benzylpiperidin-3-olHCID 580168704-Chloro-6-(2-fluorophenyl)-5-(4-methoxyphenyl)furo[2,3-d]pyrimidine

Product 1

HCID 671602904-{[(3R)-1-Benzylpiperidin-3-yl]oxy}-6-(2-fluorophenyl)-5-(4-methoxyphenyl)furo[2,3-d]pyrimidine

Reagents, catalysts & solvents 3

HCID 67553Tetrabutylammonium IodideCatalystHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

Dissolve 1037 mg (5.37 mmol) of (3R)-1-benzylpiperidin-3-ol [H. Tomori, Bull. Chem. Soc. Jpn. 69, 1, 207-216 (1996)] in 10 ml of THF and add 268 mg (6.71 mmol) of sodium hydride (60% in mineral oil). After 10 minutes, add a solution of 2000 mg (5.64 mmol) of 4-chloro-6-(2-fluorophenyl)-5-(4-methoxyphenyl)furo[2,3-d]pyrimidine in 10 ml of THF and 99 mg (0.27 mmol) of tetra-n-butylammonium iodide. Heat the reaction mixture under reflux for 16 hours. Then add 100 ml of water and 100 ml of ethyl acetate. Remove the organic phase and wash with 50 ml of 1N hydrochloric acid and 100 ml of satd. sodium chloride solution. Re-extract the aqueous phase with 50 ml of ethyl acetate, dry the combined organic extracts over sodium sulphate, filter and concentrate under reduced pressure. 2645 mg (89% of theory, 92% purity) of the desired product are obtained.

Workup

  1. temperatureHeat the reaction mixture
  2. temperatureunder reflux for 16 hours
  3. customRemove the organic phase
  4. washwash with 50 ml of 1N hydrochloric acid and 100 ml of satd
  5. dry with materialRe-extract the aqueous phase with 50 ml of ethyl acetate, dry the combined organic extracts over sodium sulphate
  6. filtrationfilter
  7. concentrationconcentrate under reduced pressure

Sources & evidence

ORD record
ord-19db67608c9c4062a6182399b5960012
Source dataset
uspto-grants-2012_12
Patent number
US08324222B2

Reaction notes

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