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Water → Tert-butyl 4-(3-(hydroxymethyl)-1-(4-(methylsulfonyl)phenyl)-6-oxo-1,6-dihydropyridazin-4-yloxy)piperidine-1-carboxylate

HRID 386577
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HRID 386577 반응식
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:15]2[C:16]([C:32](OC)=[O:33])=[N:17][N:18]([C:22]3[CH:27]=[CH:26][C:25]([S:28]([CH3:31])(=[O:30])=[O:29])=[CH:24][CH:23]=3)[C:19](=[O:21])[CH:20]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[BH4-].[Na+].CCOC(C)=O.O>C1COCC1.CO>[OH:33][CH2:32][C:16]1[C:15]([O:14][CH:11]2[CH2:10][CH2:9][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[CH2:13][CH2:12]2)=[CH:20][C:19](=[O:21])[N:18]([C:22]2[CH:23]=[CH:24][C:25]([S:28]([CH3:31])(=[O:30])=[O:29])=[CH:26][CH:27]=2)[N:17]=1
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참가 물질

6

반응물 4

HCID 962WaterHCID 8857Ethyl AcetateHCID 4311764Sodium borohydrideHCID 44621631Methyl 4-(1-(tert-butoxycarbonyl)piperidin-4-yloxy)-1-(4-(methylsulfonyl)phenyl)-6-oxo-1,6-dihydropyridazine-3-carboxylate

생성물 1

HCID 67072635Tert-butyl 4-(3-(hydroxymethyl)-1-(4-(methylsulfonyl)phenyl)-6-oxo-1,6-dihydropyridazin-4-yloxy)piperidine-1-carboxylate수율 95.9%

시약·촉매·용매 1

HCID 21899815MeOH tetrahydrofuran용매

실험 절차

To a stirring solution of methyl 4-(1-(tert-butoxycarbonyl)piperidin-4-yloxy)-1-(4-(methylsulfonyl)phenyl)-6-oxo-1,6-dihydropyridazine-3-carboxylate (example 18) (254 mg, 0.5 mmol) in THF/MeOH (1:1) (10 mL) at room temperature under argon was added NaBH4 (95 mg, 2.5 mmol) at 0° C. in an ice bath under argon carefully. The reaction mixture was allowed to warm to room temperature gradually and stirred overnight. EtOAc (20 mL) and water (20 mL) were added to the reaction mixture. Layers were separated. Organic layer were washed with water (15 mL), and brine (15 mL). Organic phase was dried (MgSO4), filtered and concentrated. The crude product was dissolved in a small amount of DCM (˜2 ml) and loaded onto a 40 g ISCO silica gel column which was eluted with a 20 min gradient from 20% to 100% EtOAc/Hexanes. 230 mg (95%) of tert-butyl 4-(3-(hydroxymethyl)-1-(4-(methylsulfonyl)phenyl)-6-oxo-1,6-dihydropyridazin-4-yloxy)piperidine-1-carboxylate was obtained as a white solid MS (ESI) 434 (M+H-tBu).

후처리

  1. customLayers were separated
  2. washOrganic layer were washed with water (15 mL), and brine (15 mL)
  3. dry with materialOrganic phase was dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. dissolutionThe crude product was dissolved in a small amount of DCM (˜2 ml)
  7. washwas eluted with a 20 min gradient from 20% to 100% EtOAc/Hexanes

출처 및 근거

ORD 기록
ord-5bf456bc046748f2bce568e65e984b26
출처 데이터셋
uspto-grants-2013_02
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08372837B2

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