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

HRID 1054161Notes

Reaction equation

C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC.[O:19]=[C:20]1[NH:25][C:24]2[CH:26]=[C:27]([C:30]([OH:32])=O)[CH:28]=[CH:29][C:23]=2[O:22][CH2:21]1.[CH2:33]([O:35][C:36](=[O:48])[CH2:37][CH:38]1[NH:43][C:42]2[CH:44]=[CH:45][CH:46]=[CH:47][C:41]=2[O:40][CH2:39]1)[CH3:34]>CCOC(C)=O>[O:19]=[C:20]1[NH:25][C:24]2[CH:26]=[C:27]([C:30]([N:43]3[C:42]4[CH:44]=[CH:45][CH:46]=[CH:47][C:41]=4[O:40][CH2:39][CH:38]3[CH2:37][C:36]([O:35][CH2:33][CH3:34])=[O:48])=[O:32])[CH:28]=[CH:29][C:23]=2[O:22][CH2:21]1

Participants

Conditions

Temperature: 75 °C

Procedure

T3P (50% solution in EtOAc, 132.4 g, 0.208 mol) was added to 3-oxo-3,4-dihydro-2H-1,4-benzoxazine-6-carboxylic acid (22.1 g, 0.114 mol), ethyl-2-(3,4-dihydro-2H-1,4-benzoxazin-3-yl)acetate (23.0 g, 0.104 mol) and TEA (57.9 mL, 0.416 mol) in EtOAc (139 mL) at rt. The resulting mixture was stirred at 75° C. for 16 h. The resulting solution was diluted with 800 mL of EtOAc and washed with aq. sat. NaHCO3 solution (300 mL), 0.5 M HCl solution (300 mL) and brine (300 mL). The organic phase was dried over anhydrous Na2SO4, filtered and evaporated to afford crude product. The crude product was purified by re-crystallization from MeOH to afford the title compound (14.5 g, 35%) as a white solid.

Workup

washwashed with aq. sat. NaHCO3 solution (300 mL), 0.5 M HCl solution (300 mL) and brine (300 mL)
dry with materialThe organic phase was dried over anhydrous Na2SO4
filtrationfiltered
customevaporated
customto afford crude product
customThe crude product was purified by re-crystallization from MeOH

Sources & evidence

ORD record: ord-19a9a3e9c6e74b3e92e09e7e477da0b1
Source dataset: uspto-grants-2016_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09394291B2

Reaction notes

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