Diisopropylamine → tert-Butyl 4-(1-(3-fluoro-2-pivalamidophenyl)-1-hydroxy-3-methoxy-3-oxopropan-2-yl)piperidine-1-carboxylate

HRID 1172361노트

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HRID 1172361 반응식
C(NC(C)C)(C)C.C([Li])CCC.C1CCCCC1.[CH3:19][O:20][C:21](=[O:36])[CH2:22][CH:23]1[CH2:28][CH2:27][N:26]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH2:25][CH2:24]1.[H-].[Na+].[F:39][C:40]1[CH:45]=[CH:44][CH:43]=[C:42]([CH:46]=[O:47])[C:41]=1[NH:48][C:49](=[O:54])[C:50]([CH3:53])([CH3:52])[CH3:51]>O1CCCC1>[F:39][C:40]1[C:41]([NH:48][C:49](=[O:54])[C:50]([CH3:52])([CH3:51])[CH3:53])=[C:42]([CH:46]([OH:47])[CH:22]([CH:23]2[CH2:24][CH2:25][N:26]([C:29]([O:31][C:32]([CH3:33])([CH3:35])[CH3:34])=[O:30])[CH2:27][CH2:28]2)[C:21]([O:20][CH3:19])=[O:36])[CH:43]=[CH:44][CH:45]=1

참가 물질

8

반응물 6

HCID 7912DiisopropylamineHCID 8078CyclohexaneHCID 24758Sodium hydrideHCID 1514280tert-Butyl 4-(2-methoxy-2-oxoethyl)piperidine-1-carboxylateHCID 59424313N-(2-Fluoro-6-formylphenyl)pivalamideHCID 178418339Butyllithium

생성물 1

HCID 59424341tert-Butyl 4-(1-(3-fluoro-2-pivalamidophenyl)-1-hydroxy-3-methoxy-3-oxopropan-2-yl)piperidine-1-carboxylate수율 81%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매4회

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온도
-78 °C

실험 절차

Diisopropylamine (24.2 mmol, 3.40 mL) was dissolved in tetrahydrofuran (70 mL). The mixture was cooled to −78° C. 2N Butyllithium in cyclohexane (24.40 mmoles, 12.20 mL) was added drop-wise to the reaction. The mixture was held at −78° C. with stirring on and held for 20 minutes. A solution of tert-butyl 4-(2-methoxy-2-oxoethyl)piperidine-1-carboxylate (20.21 mmoles, 5.20 g) in 15 mL tetrahydrofuran was added to the mixture drop-wise. The mixture was held at −78° C. with stirring on and held for 45 min. In a seperate flask, 60% Sodium hydride in mineral oil (24.25 mmoles, 970.00 mg) was washed with hexanes then suspended in tetrahydrofuran (50.00 mL). The mixture was cooled to 0° C. A solution of N-(2-Fluoro-6-formylphenyl)pivalamide (20.16 mmoles, 4.50 g) in 20 mL tetrahydrofuran was added to the mixture drop-wise. The mixture was held at 0° C. with stirring on and held for 1 hr. Aldehyde mixture was added to the ester mixture drop-wise over 1.25 hours. The mixture was held at −78° C. with stirring on and held for 1 hr. The reaction was quenched with aq. ammonium chloride. Mixture was warmed to room temperature then diluted with water. The mixture was extracted 2 times with ethyl acetate and the aqueous phase was discarded. The material was dried (magnesium sulfate), filtered, and concentrated to dryness. Silica gel chromatography gave the title compound as white foam in 81% yield. MS m/e (M-C4H8O2+H)+=381.2.

후처리

  1. customto the reaction
  2. customwas held at −78° C.
  3. customwas held at −78° C.
  4. stirringwith stirring on and
  5. waitheld for 45 min
  6. temperatureThe mixture was cooled to 0° C
  7. customwas held at 0° C.
  8. stirringwith stirring on and
  9. waitheld for 1 hr
  10. customwas held at −78° C.
  11. stirringwith stirring on and
  12. waitheld for 1 hr
  13. customThe reaction was quenched with aq. ammonium chloride
  14. temperatureMixture was warmed to room temperature
  15. additionthen diluted with water
  16. extractionThe mixture was extracted 2 times with ethyl acetate
  17. dry with materialThe material was dried (magnesium sulfate)
  18. filtrationfiltered
  19. concentrationconcentrated to dryness

출처 및 근거

ORD 기록
ord-7b045dba7149441e8c55a575ca308f6f
출처 데이터셋
uspto-grants-2010_11
특허 번호
US07834007B2

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