4-Methylmorpholine → HCID 11074788、化合物

HRID 1066026ノート

反応式

HRID 1066026 の反応式
[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]

参加物

8

反応物 4

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

生成物 1

HCID 11074788HCID 11074788、化合物収率 60.1%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒

実験手順

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+).

後処理

  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)

出典と根拠

ORDレコード
ord-3bb3168327344b0aa86dd8041e8726d3
出典データセット
uspto-grants-2001_06
特許番号
US06242439B1

反応ノート

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