Diethyl Pyrocarbonate → N-(4-(trifluoromethyl)-2-(piperidin-1-yl)benzyl)-2,3-dihydro-2-oxobenzo[d]oxazole-4-carboxamide

HRID 1505203Notes

Reaction equation

[O:1]=[C:2]1[NH:6][C:5]2=[C:7]([C:11]([OH:13])=O)[CH:8]=[CH:9][CH:10]=[C:4]2[O:3]1.CCOC(OC(OCC)=O)=O.[F:25][C:26]([F:42])([F:41])[C:27]1[CH:32]=[CH:31][C:30]([CH2:33][NH2:34])=[C:29]([N:35]2[CH2:40][CH2:39][CH2:38][CH2:37][CH2:36]2)[CH:28]=1>C1COCC1>[F:41][C:26]([F:25])([F:42])[C:27]1[CH:32]=[CH:31][C:30]([CH2:33][NH:34][C:11]([C:7]2[CH:8]=[CH:9][CH:10]=[C:4]3[O:3][C:2](=[O:1])[NH:6][C:5]=23)=[O:13])=[C:29]([N:35]2[CH2:40][CH2:39][CH2:38][CH2:37][CH2:36]2)[CH:28]=1

Participants

Conditions

Temperature: 80 °C

Procedure

2,3-dihydro-2-oxobenzo[d]oxazole-4-carboxylic acid 21 (560 mg, 3.1 mmol) was dissolved in 20 ml of THF and at 0° C. DEPC (0.55 ml, 1.2 equiv) and amine 2c (964 mg, 1.2 equiv.) were added to the solution. The mixture was warmed at 80° C. overnight, then evaporated and the crude was dissolved in AcOEt (30 ml) and washed with water (1×20 ml) and brine. The organic phase was dried over sodium sulfate and concentrated under vacuum. The purification of the crude residue by chromatographic column using AcOEt 4/petroleum ether 6 as eluant gave 250 mg of a pale yellow solid. Yield=19% 1HNMR (DMSO, 200 MHz) δ 4.58 (2H, d, J=5.8 Hz), 7.14 (1H, t, J=8 Hz), 7.41 (4H, m), 7.68 (1H, dd, J=8 Hz, J′=0.8 Hz), 9.20 (1H, bt), 11.59 (1H, bs); [M+1] 420.2 (C21H20F3N3O3 requires 419.4).

Workup

customevaporated
dissolutionthe crude was dissolved in AcOEt (30 ml)
washwashed with water (1×20 ml) and brine
dry with materialThe organic phase was dried over sodium sulfate
concentrationconcentrated under vacuum
customThe purification of the crude residue by chromatographic column

Sources & evidence

ORD record: ord-3a51ea9d376f4d6ba0dd798276c379d9
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09216975B2

Reaction notes

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