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

HRID 488367

Reaction equation

HRID 488367 reaction equation
[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

Participants

6

Reactant 4

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-c53695e39dce40c6adf05537108b9264
Source dataset
uspto-grants-2005_12
Patent number
US06972286B2

Linked notes

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