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

HRID 2189076노트

반응식

HRID 2189076 반응식
[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

참가 물질

8

반응물 4

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

생성물 1

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

시약·촉매·용매 3

HCID 67553Tetrabutylammonium Iodide촉매HCID 8028Tetrahydrofuran용매2회HCID 8857Ethyl Acetate용매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-19db67608c9c4062a6182399b5960012
출처 데이터셋
uspto-grants-2012_12
특허 번호
US08324222B2

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