Nitric Acid → HCID 86724398, compound

HRID 707687Notes

Reaction equation

[F:1][CH:2]([F:21])[C@@H:3]1[C@@H:11]2[C@@:6]([C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([F:19])[C:14]=3[F:20])([N:7]=[C:8]([NH2:12])[S:9][CH2:10]2)[CH2:5][O:4]1.S(=O)(=O)(O)O.[N+:27]([O-])([OH:29])=[O:28].C([O-])(O)=O.[Na+]>C(O)(C(F)(F)F)=O>[F:20][C:14]1[C:15]([F:19])=[CH:16][C:17]([N+:27]([O-:29])=[O:28])=[CH:18][C:13]=1[C@:6]12[CH2:5][O:4][C@H:3]([CH:2]([F:1])[F:21])[C@H:11]1[CH2:10][S:9][C:8]([NH2:12])=[N:7]2

Participants

Conditions

Temperature: 0 °C

Procedure

(4aS,5S,7aS)-5-(difluoromethyl)-7a-(2,3-difluorophenyl)-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-2-amine, obtained in Preparation Example 1-(9), (565 mg) was dissolved in TFA (3 mL), and the solution was cooled to 0° C. Sulfuric acid (conc., 0.8 mL) was added, followed by fuming nitric acid (0.08 mL) dropwise over 20 mins. After stirring at 0° C. for 90 min, the reaction mixture carefully neutralized with NaHCO3 (sat., aq., 50 mL) and extracted with EtOAc (3×100 mL), and the combined organic portions dried over MgSO4 and evaporated. The residue was purified by silica gel column chromatography (0% to 80% EtOAc in hexanes) to afford the title compound (700 mg, purity approx. 80%) which was used in the subsequent step without purification. 1H NMR (400 MHz, CDCl3) δ ppm 3.04 (dd, J=14.0, 3.9 Hz, 1H), 3.23-3.31 (m, 1H), 3.59 (d, J=3.0 Hz, 1H), 4.23 (d, J=9.9 Hz, 1H), 4.44-4.60 (m, 2H), 6.02 (t, J=57.6 Hz, 1H), 8.02-8.26 (m, 2H)

Workup

extractionextracted with EtOAc (3×100 mL)
dry with materialthe combined organic portions dried over MgSO4
customevaporated
customThe residue was purified by silica gel column chromatography (0% to 80% EtOAc in hexanes)

Sources & evidence

ORD record: ord-407b0d631da44d6983ae254660e79cf4
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09175013B2

Reaction notes

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