1,8-Diazabicyclo(5.4.0)undec-7-ene → HCID 70495591, compound

HRID 2045852Notes

Reaction equation

[F:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][C:3]=1[C@:9]12[CH2:17][O:16][C@H:15]([C:18]([F:21])([F:20])[F:19])[C@H:14]1[CH2:13][S:12][C:11]([NH:22]C(=O)C1C=CC=CC=1)=[N:10]2.N12CCCN=C1CCCCC2>CO>[F:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][C:3]=1[C@:9]12[CH2:17][O:16][C@H:15]([C:18]([F:20])([F:19])[F:21])[C@H:14]1[CH2:13][S:12][C:11]([NH2:22])=[N:10]2

Participants

Conditions

Temperature: 80 °C

Procedure

N-((4aS,5S,7aS)-7a-(2,3-Difluorophenyl)-5-(trifluoromethyl)-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-2-yl)benzamide (2.00 g) was dissolved in methanol (250 mL), 1,8-diazabicyclo[5.4.0]undec-7-ene (1.53 g) was added, and the solution was heated to reflux (heating block temperature 80° C.). After 3 h, the reaction mixture was concentrated under reduced pressure, diluted with water (100 mL) and extracted with EtOAc (3×100 mL). The combined organic portions were dried over MgSO4, evaporated, and the residue purified by silica gel column chromatography (0% to 50% EtOAc in hexanes) to afford the title compound (1.42 g). 1H NMR (400 MHz, CDCl3) δ ppm 2.86 (dd, J=13.6, 3.8 Hz, 1H), 3.15 (dd, J=13.8, 3.2 Hz, 1H), 3.27-3.42 (m, 1 H), 3.93 (dd, J=8.2, 1.9 Hz, 1H), 4.39-4.78 (m, 4H), 6.96-7.25 (m, 3H)

Workup

temperaturethe solution was heated
temperatureto reflux
concentrationthe reaction mixture was concentrated under reduced pressure
additiondiluted with water (100 mL)
extractionextracted with EtOAc (3×100 mL)
dry with materialThe combined organic portions were dried over MgSO4
customevaporated
customthe residue purified by silica gel column chromatography (0% to 50% EtOAc in hexanes)

Sources & evidence

ORD record: ord-b1954ce3c54b44c0993487c606c1a8ac
Source dataset: uspto-grants-2013_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08592408B2

Reaction notes

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