Water → HCID 86727345, compound

HRID 518991Notes

Reaction equation

HRID 518991 reaction equation
[CH2:1]([O:3][C:4](=[O:21])[C:5]([CH2:19]C)([N:7]1[C:12]2[CH:13]=[C:14]([OH:17])[CH:15]=[CH:16][C:11]=2[O:10][CH2:9][C:8]1=[O:18])C)[CH3:2].[C:22]([O:26][C:27]([N:29]1[CH2:32][CH:31](OS(C)(=O)=O)[CH2:30]1)=[O:28])([CH3:25])([CH3:24])[CH3:23].C([O-])([O-])=O.[Cs+].[Cs+].O>CN(C=O)C>[C:22]([O:26][C:27]([N:29]1[CH2:32][CH:31]([O:17][C:14]2[CH:15]=[CH:16][C:11]3[O:10][CH2:9][C:8](=[O:18])[N:7]([CH:5]([C:4]([O:3][CH2:1][CH3:2])=[O:21])[CH3:19])[C:12]=3[CH:13]=2)[CH2:30]1)=[O:28])([CH3:25])([CH3:23])[CH3:24]

Participants

6

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 10753243Tert-butyl 3-(methanesulfonyloxy)azetidine-1-carboxylateHCID 86727346Ethyl 2-(6-hydroxy-3-oxo-2,3-dihydro-benzo[1,4]oxazin-4-yl)-propionic acid ethyl ester

Product 1

HCID 86727345HCID 86727345, compoundYield 41%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of ethyl 2-(6-hydroxy-3-oxo-2,3-dihydro-benzo[1,4]oxazin-4-yl)-propionic acid ethyl ester (1.08 g, 4.07 mmol), 3-methanesulfonyloxy-azetidine-1-carboxylic acid tert-butyl ester (1.12 g, 4.48 mmol) and Cs2CO3 (2.65 g, 8.12 mmol) in DMF (20 mL) was stirred at 90° C. for 3 h. The reaction mixture was cooled to ambient temperature and poured into water (150 mL). The aqueous mixture was extracted with EtOAc (3×20 mL) and the combined organic phase was washed with brine (50 mL), dried over anhydrous Na2SO4, filtered and evaporated in vacuo. The residue was purified by column chromatography on silica gel (eluting with 10% EtOAc in petroleum ether) to give 3-[4-(1-ethoxycarbonyl-ethyl)-3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yloxy]-azetidine-1-carboxylic acid tert-butyl ester as a white solid (0.7 g, 41%). 1H NMR (CDCl3, 400 MHz): δ 6.94 (d, J=8.4 Hz, 1H), 6.30 (m, 2H), 5.30 (q, J=7.2 Hz, 1H), 4.78 (m, 1H), 4.59 (d, J=15.2 Hz, 2H), 4.27 (m, 4H), 3.95 (m, 2H), 1.62 (d, J=7.2 Hz, 3H), 1.45 (s, 9H), 1.21 (t, J=7.2 Hz, 3H).

Workup

  1. temperatureThe reaction mixture was cooled to ambient temperature
  2. extractionThe aqueous mixture was extracted with EtOAc (3×20 mL)
  3. washthe combined organic phase was washed with brine (50 mL)
  4. dry with materialdried over anhydrous Na2SO4
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. customThe residue was purified by column chromatography on silica gel (eluting with 10% EtOAc in petroleum ether)

Sources & evidence

ORD record
ord-485925f63a614192b8304628c6f29482
Source dataset
uspto-grants-2015_08
Patent number
US09115151B2

Reaction notes

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