Acetic Acid → (+/-) Tert-butyl 3-(hydroxymethyl)-4-(oxetan-3-yl)piperazine-1-carboxylate

HRID 921686노트

반응식

HRID 921686 반응식
[OH:1][CH2:2][CH:3]1[NH:8][CH2:7][CH2:6][N:5]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:4]1.[O:16]1[CH2:19][C:18](=O)[CH2:17]1.CC(O)=O.C([BH3-])#N.[Na+]>C(Cl)Cl.CO>[OH:1][CH2:2][CH:3]1[N:8]([CH:18]2[CH2:19][O:16][CH2:17]2)[CH2:7][CH2:6][N:5]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:4]1

참가 물질

7

반응물 4

HCID 176Acetic AcidHCID 5003444Sodium cyanoborohydrideHCID 150242543-OxetanoneHCID 223865084-N-Boc-2-hydroxymethylpiperazine

생성물 1

HCID 86708556(+/-) Tert-butyl 3-(hydroxymethyl)-4-(oxetan-3-yl)piperazine-1-carboxylate수율 62.1%

시약·촉매·용매 2

HCID 887Methanol용매HCID 6344Dichloromethane용매

실험 절차

(+/−) Tert-butyl 3-(hydroxymethyl)piperazine-1-carboxylate (3.07 g, 14.19 mmol), oxetan-3-one (1.820 mL, 28.4 mmol), AcOH (1.625 mL, 28.4 mmol), and 4 Å molecular sieves were taken up in DCM (16 mL) and MeOH (16.00 mL), and the reaction was stirred at room temperature overnight. Sodium cyanoborohydride (4.46 g, 71.0 mmol) was added and the reaction was stirred at room temperature for 2 h. The reaction mixture was filtered through celite, rinsing with MeOH. The solvent was removed in vacuo and the material was quenched with 2M K3PO4 solution, and then extracted 2× with EtOAc. The organic layers were combined, dried over Na2SO4, filtered, and concentrated. The material was purified by flash column chromatography (0-8% MeOH/DCM). (+/−) Tert-butyl 3-(hydroxymethyl)-4-(oxetan-3-yl)piperazine-1-carboxylate (2.40 g) was obtained as a colorless oil.

후처리

  1. filtrationThe reaction mixture was filtered through celite
  2. washrinsing with MeOH
  3. customThe solvent was removed in vacuo
  4. customthe material was quenched with 2M K3PO4 solution
  5. extractionextracted 2× with EtOAc
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe material was purified by flash column chromatography (0-8% MeOH/DCM)

출처 및 근거

ORD 기록
ord-3af88a335e03447396d0593d75988f7a
출처 데이터셋
uspto-grants-2016_03
특허 번호
US09273057B2

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