Methanol → N-[[(5S)-3-(3,4-dihydro-1H-2-benzopyran-6-yl)-2-oxo-5-oxazolidinyl]methyl]acetamide

HRID 488367

반응식

HRID 488367 반응식
[CH2:1]1[C:6]2[CH:7]=[CH:8][C:9]([NH:11]C(=O)OCC3C=CC=CC=3)=[CH:10][C:5]=2[CH2:4][CH2:3][O:2]1.CO.O(C(C)(C)C)[Li].[C:30]([O:33][C@H:34]([CH2:40]Cl)[CH2:35][NH:36][C:37](=[O:39])[CH3:38])(=[O:32])C>CN(C=O)C>[CH2:1]1[C:6]2[CH:7]=[CH:8][C:9]([N:11]3[CH2:40][C@H:34]([CH2:35][NH:36][C:37](=[O:39])[CH3:38])[O:33][C:30]3=[O:32])=[CH:10][C:5]=2[CH2:4][CH2:3][O:2]1

참가 물질

6

반응물 4

HCID 887MethanolHCID 7357675(2S)-1-Acetamido-3-chloropropan-2-yl acetateHCID 86594253Phenylmethyl (3,4-dihydro-1H-2-benzopyran-6-yl)carbamateHCID 178506942HCID 178506942, 화합물

생성물 1

HCID 60054144N-[[(5S)-3-(3,4-dihydro-1H-2-benzopyran-6-yl)-2-oxo-5-oxazolidinyl]methyl]acetamide수율 50.5%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

A solution of phenylmethyl (3,4-dihydro-1H-2-benzopyran-6-yl)carbamate (Step 1, 1.60 g, 5.65 mmol) and MeOH (0.458 mL, 11.3 mmol) in dry DMF (5.6 mL) under N2 is cooled in an ice bath and treated with LiOtBu (1M in THF, 16.95 mL, 16.95 mmol) dropwise over 2 mins. Then, the (1S)-2-(acetylamino)-1-(chloromethyl)ethyl acetate (2.19 g, 11.3 mmol) is added all at once, the cooling bath is removed and the mixture is stirred at ambient temperature for 2.75 days and is then diluted with H2O (20 mL) and extracted with EtOAc (4×50 mL). The combined organic phase is washed with brine (25 mL), dried over MgSO4 and concentrated under reduced pressure, and the residue is chromatographed on a Flash 40M silica gel (90 g, 32-63 μm) cartridge, eluting with a gradient of MeOH/CH2Cl2 (1/99-2/98). Those fractions with an Rf=0.23 by TLC (MeOH/CHCl3, 5/95) are pooled and concentrated and the product triturated with EtOAc to give 828 mg (50%) of the title compound as a white solid, mp 142-145° C. [α]25D=−24° (c 1.01, DMSO).

후처리

  1. customis removed
  2. additionis then diluted with H2O (20 mL)
  3. extractionextracted with EtOAc (4×50 mL)
  4. washThe combined organic phase is washed with brine (25 mL)
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated under reduced pressure
  7. customthe residue is chromatographed on a Flash 40M silica gel (90 g, 32-63 μm) cartridge
  8. washeluting with a gradient of MeOH/CH2Cl2 (1/99-2/98)
  9. concentrationconcentrated
  10. customthe product triturated with EtOAc

출처 및 근거

ORD 기록
ord-c53695e39dce40c6adf05537108b9264
출처 데이터셋
uspto-grants-2005_12
특허 번호
US06972286B2

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