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

HRID 1054160Notes

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.[O:33]1[C:38]2[CH:39]=[CH:40][CH:41]=[CH:42][C:37]=2[NH:36][CH:35]([CH2:43][C:44]([O:46][CH3:47])=[O:45])[CH2:34]1>CCOC(C)=O>[O:19]=[C:20]1[NH:25][C:24]2[CH:26]=[C:27]([C:30]([N:36]3[C:37]4[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=4[O:33][CH2:34][CH:35]3[CH2:43][C:44]([O:46][CH3:47])=[O:45])=[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, 61.5 g, 96.6 mmol) was added to 3-oxo-3,4-dihydro-2H-1,4-benzoxazine-6-carboxylic acid (10.3 g, 53.1 mmol), methyl 3,4-dihydro-2H-1,4-benzoxazin-3-ylacetate (Intermediate 2, 10.0 g, 48.3 mmol) and TEA (26.8 mL, 193.2 mmol) in EtOAc (125 mL) at rt. The resulting mixture was stirred at 75° C. for 16 h. The resulting solution was diluted with 350 mL of EtOAc and washed with sat. aq. NaHCO3 solution (160 mL), 0.5 M HCl solution (160 mL) and brine (160 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 (10.1 g, 55%) as a white solid.

Workup

washwashed with sat. aq. NaHCO3 solution (160 mL), 0.5 M HCl solution (160 mL) and brine (160 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-9654556a980e49c5994b4bc23e9714a5
Source dataset: uspto-grants-2016_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09394291B2

Reaction notes

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