Ethyl Acetate → 6-Methoxy-2-(trifluoromethyl)pyridin-3-amine

HRID 1297287Notes

Reaction equation

[CH3:1][O:2][C:3]1[N:8]=[C:7]([C:9]([F:12])([F:11])[F:10])[C:6]([N+:13]([O-])=O)=[CH:5][CH:4]=1.O.O.[Sn](Cl)Cl.[OH-].[Na+].C(OCC)(=O)C>C(O)C>[CH3:1][O:2][C:3]1[N:8]=[C:7]([C:9]([F:10])([F:11])[F:12])[C:6]([NH2:13])=[CH:5][CH:4]=1

Participants

Conditions

Temperature: 70 °C

Procedure

To a solution of 6-methoxy-3-nitro-2-(trifluoromethyl)pyridine (3.61 g) in 95% Ethyl alcohol (162 ml) was added tin(II) chloride dihydrate. It was heated to 70° C. for 3 hr. After it was cooled to room temperature, it was poured over ice water and adjusted to pH 11 with 2N NaOH. It was stirred well with ethyl acetate and filtered through celite. The organic phase was separated, washed with brine, dried (MgSO4), filtered and concentrated. The flash column chromatography (SiO2, 3˜8% EtOAc in heptane) gave the title compounds (2.20 g, 71%). 1H NMR (CDCl3) δ 3.81, 6.70, 7.05; 19F NMR (CDCl3) δ 65.73; IR (liq.) 2434 (w), 2389, 2272, 2229, 2174, 1488 (s), 1436 (s), 1426 (s), 1276 (s), 1170 (s), 1102 (s, b), 1050 (s), 1024 (s), 740 (s), 658 (s) cm−1 HRMS (ESI) calcd for C7H7N2OF3+H1 193.0589. found 193.0581. Anal. Calcd for C7H7F3N2O: C, 43.76; H, 3.67; N, 14.58; F, 29.66. Found: C, 43.61; H, 3.49; N, 14.49.

Workup

temperatureAfter it was cooled to room temperature
filtrationfiltered through celite
customThe organic phase was separated
washwashed with brine
dry with materialdried (MgSO4)
filtrationfiltered
concentrationconcentrated

Sources & evidence

ORD record: ord-fb126a3ec82b4487816b8326641a7222
Source dataset: uspto-grants-2007_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07250418B2

Reaction notes

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