Acetic Acid → 1-[2-[2-(3-Hydroxy-1-azetidinyl)ethyl]phenyl]-2-piperidinone

HRID 2178532노트

반응식

HRID 2178532 반응식
[O:1]=[C:2]1[CH2:7][CH2:6][CH2:5][CH2:4][N:3]1[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[CH2:14][CH:15]=O.Cl.[NH:18]1[CH2:21][CH:20]([OH:22])[CH2:19]1.C(O)(=O)C.[BH3-]C#N.[Na+]>CO.[Cl-].[Na+].O.ClCCl.O>[OH:22][CH:20]1[CH2:21][N:18]([CH2:15][CH2:14][C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=2[N:3]2[CH2:4][CH2:5][CH2:6][CH2:7][C:2]2=[O:1])[CH2:19]1

참가 물질

9

반응물 4

HCID 176Acetic AcidHCID 27592903-Hydroxyazetidine hydrochlorideHCID 5003444Sodium cyanoborohydrideHCID 89500863[2-(2-Oxopiperidin-1-yl)phenyl]acetaldehyde

생성물 1

HCID 895006261-[2-[2-(3-Hydroxy-1-azetidinyl)ethyl]phenyl]-2-piperidinone수율 12.7%

시약·촉매·용매 4

HCID 887Methanol용매HCID 962Water용매HCID 6344Dichloromethane용매HCID 57417360Sodium chloride; water용매

실험 절차

To [2-(2-oxopiperidin-1-yl)phenyl]acetaldehyde a3-1 (1.32 g, 6.09 mmol, 1 eq) in methanol (50 ml) is added azetidin-3-ol hydrochloride al 1-0 (0.76 g, 6.96 mmol, 1.14 eq). After stirring at room temperature for approximately 30 minutes, acetic acid (522 μl, 9.13 mmol, 1.5 eq), then NaBH3CN (1.15 g, 18.26 mmol, 3 eq) are added. The reaction mixture is stirred overnight at room temperature, then filtered and loaded on an ion exchange acidic resin cartridge prewashed with methanol. The cartridge is then washed with approximately 3 column volumes of methanol, then eluted with 3 column volumes of 1M ammonia in methanol. This eluate is evaporated to dryness. To the residue obtained is added water (50 ml) and dichloromethane (50 ml). After vigorous shaking and addition of brine, the 2 phases are separated. The organic phase is washed with water (50 ml). The aqueous phases are pooled and washed 3 times with iPrOH/CH2Cl2 (25 ml/50 ml). The organic phases are combined, evaporated to dryness to give 212.6 mg of 1-{2-[2-(3-hydroxyazetidin-1-yl)ethyl]phenyl}piperidin-2-one a11-1 (212.6 mg, 0.775 mmole if assumed pure, 12.7% yield), which is used in next step without any further purification.

후처리

  1. stirringThe reaction mixture is stirred overnight at room temperature
  2. filtrationfiltered
  3. washThe cartridge is then washed with approximately 3 column volumes of methanol
  4. washeluted with 3 column volumes of 1M ammonia in methanol
  5. customThis eluate is evaporated to dryness
  6. customTo the residue obtained
  7. stirringAfter vigorous shaking
  8. customthe 2 phases are separated
  9. washThe organic phase is washed with water (50 ml)
  10. washwashed 3 times with iPrOH/CH2Cl2 (25 ml/50 ml)
  11. customevaporated to dryness

출처 및 근거

ORD 기록
ord-c1829c794e97424aae433a7868832205
출처 데이터셋
uspto-grants-2015_06
특허 번호
US09067930B2

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