4-Methylmorpholine → HCID 11074788, 화합물

HRID 1066026노트

반응식

HRID 1066026 반응식
[Si:1]([N:8]1[C:11](=[O:12])[CH2:10][C@@H:9]1[C:13](O)=[O:14])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].CN1CCOCC1.ClC(OCC(C)C)=O.[BH4-].[Na+]>C1COCC1.O.CCOC(C)=O>[Si:1]([N:8]1[C@@H:9]([CH2:13][OH:14])[CH2:10][C:11]1=[O:12])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]

참가 물질

8

반응물 4

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 2733822(R)-1-(tert-Butyldimethylsilyl)-4-oxoazetidine-2-carboxylic acidHCID 4311764Sodium borohydride

생성물 1

HCID 11074788HCID 11074788, 화합물수율 60.1%

시약·촉매·용매 3

HCID 962Water용매HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매

실험 절차

To a solution of 1-(tert-butyldimethylsilyl)-4-oxoazetidine-2(R)-carboxylic acid (15.0 g, 65.40 mmol) in THF (367 mL) at 0°, was added N-methylmorpholine (7.2 mL, 65.40 mmol) and isobutyl chloroformate (8.5 mL, 65.40 mmol). After stirring for 1.5 h at 0° a solution of NaBH4 (9.9 g, 261.61 mmol) in H2O (98 mL) was added portionwise. The reaction was stirred for 45 min, then diluted with EtOAc and quenched with aqueous HCl solution (10%) to pH 5-6. The organic phase was collected and the aqueous phase was extracted twice with EtOAc. The combined organic layers were washed with saturated aqueous NaHCO3 and brine, dried (MgSO4), filtered and concentrated. The residual oil was purified by flash chromatography (SiO2, eluent:gradient 25% to 50% EtOAc/hexane) to provide 1-(tert-butyldimethylsilyl)-4(R)-(hydroxymethyl)azetidin-2-one (8.46 g, 60% yield) as a white solid. 1H-NMR (400 MHz, CDCl3) δ3.74-3.69 (m, 1H), 3.65-3.56 (m, 2H), 3.1-2.98 (m, 1H), 2.81-2.76 (m, 1H), 2.01 (s, 1H), 0.89 (s, 9H), 0.18 (s, 3H), 0.16 (s, 3H). FAB MS m/z 216.2 (MH+).

후처리

  1. additionwas added portionwise
  2. customquenched with aqueous HCl solution (10%) to pH 5-6
  3. customThe organic phase was collected
  4. extractionthe aqueous phase was extracted twice with EtOAc
  5. washThe combined organic layers were washed with saturated aqueous NaHCO3 and brine
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residual oil was purified by flash chromatography (SiO2, eluent:gradient 25% to 50% EtOAc/hexane)

출처 및 근거

ORD 기록
ord-3bb3168327344b0aa86dd8041e8726d3
출처 데이터셋
uspto-grants-2001_06
특허 번호
US06242439B1

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