Methanamine, N-methoxy-, hydrochloride (1:1) → N-Methoxy-N-methyl-3-(1,1,2,2-tetrafluoroethoxy)benzamide

HRID 2274528Notes

Reaction equation

[F:1][C:2]([F:16])([O:6][C:7]1[CH:8]=[C:9]([CH:13]=[CH:14][CH:15]=1)[C:10]([OH:12])=O)[CH:3]([F:5])[F:4].CCN(C(C)C)C(C)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.Cl.[CH3:54][O:55][NH:56][CH3:57]>CN(C=O)C>[CH3:54][O:55][N:56]([CH3:57])[C:10](=[O:12])[C:9]1[CH:13]=[CH:14][CH:15]=[C:7]([O:6][C:2]([F:1])([F:16])[CH:3]([F:4])[F:5])[CH:8]=1

Participants

Conditions

Temperature: 25 °C

Procedure

3-(1,1,2,2-tetrafluoroethoxy)benzoic acid (10 g, 42.0 mmol) was dissolved in DMF (200 mL) and Hunig's Base (20.54 mL, 118 mmol). Benzotriazol-1-yl-oxy-tris-(dimethylamino)phosphonium hexafluorophosphate (BOP, 27.9 g, 63.0 mmol) and N-methoxy-N-methylamine hydrochloride (4.51 g, 46.2 mmol) were added to the reaction flask, and the resulting reaction mixture was stirred at 25° C. overnight. Crude reaction mixture was concentrated and purified on a silica gel column (340 g cartridge 0-10% EtOAc/Hexanes gradient) to afford N-methoxy-N-methyl-3-(1,1,2,2-tetrafluoroethoxy)benzamide. 1H NMR (400 MHz, CDCl3) δ 3.38 (s, 3H), 3.57 (s, 3H), 5.95 (t, J=52.9, 2.9 Hz, 1H), 7.33 (d, J=8.1 Hz, 1H), 7.45 (t, J=7.9 Hz, 1H), 7.58 (s, 1H), 7.63 (d, J=7.7 Hz, 1H).

Workup

customthe resulting reaction mixture
customCrude reaction mixture
concentrationwas concentrated
custompurified on a silica gel column (340 g cartridge 0-10% EtOAc/Hexanes gradient)

Sources & evidence

ORD record: ord-b7ad90db5aff472b8a2847876db54a1f
Source dataset: uspto-grants-2015_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09126976B2

Reaction notes

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