Propylphosphonic anhydride → Ethyl {7-chloro-4-[(3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl)carbonyl]-3,4-dihydro-2H-1,4-benzoxazin-3-yl}acetate

HRID 1054170Notes

Reaction equation

[Cl:1][C:2]1[CH:17]=[CH:16][C:5]2[NH:6][CH:7]([CH2:10][C:11]([O:13][CH2:14][CH3:15])=[O:12])[CH2:8][O:9][C:4]=2[CH:3]=1.[O:18]=[C:19]1[NH:24][C:23]2[CH:25]=[C:26]([C:29](O)=[O:30])[CH:27]=[CH:28][C:22]=2[O:21][CH2:20]1.C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC>CCOC(C)=O>[Cl:1][C:2]1[CH:17]=[CH:16][C:5]2[N:6]([C:29]([C:26]3[CH:27]=[CH:28][C:22]4[O:21][CH2:20][C:19](=[O:18])[NH:24][C:23]=4[CH:25]=3)=[O:30])[CH:7]([CH2:10][C:11]([O:13][CH2:14][CH3:15])=[O:12])[CH2:8][O:9][C:4]=2[CH:3]=1

Participants

Conditions

Temperature: 160 °C

Procedure

Ethyl (7-chloro-3,4-dihydro-2H-1,4-benzoxazin-3-yl)acetate (Intermediate 20, 0.67 g, 2.62 mmol), 3-oxo-3,4-dihydro-2H-1,4-benzoxazine-6-carboxylic acid (0.607 g, 3.14 mmol), and TEA (1.090 mL, 7.86 mmol) were dissolved in EtOAc (15 mL). Then T3P (50 wt. % in EtOAc, 3.12 mL, 5.24 mmol) was added and the mixture was heated in a microwave reactor for 2 h at 160° C. EtOAc (100 mL) was added and the mixture was washed with sat. aq. NaHCO3 (100 mL), 1 M HCl (100 mL) and brine (100 mL). The mixture was dried by passage through a phase separator. Concentration under reduced pressure gave 1.14 g of an oil that was purified by flash chromatography on silica gel using a gradient from 12% to 100% of EtOAc in heptane as eluent. Concentration to dryness gave the title compound (0.530 g, 46.9%).

Workup

washthe mixture was washed with sat. aq. NaHCO3 (100 mL), 1 M HCl (100 mL) and brine (100 mL)
customThe mixture was dried by passage through a phase separator
concentrationConcentration under reduced pressure

Sources & evidence

ORD record: ord-08bca519ba2843c3ab550c96d8563b79
Source dataset: uspto-grants-2016_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09394291B2

Reaction notes

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