Toluene → Methyl 6-amino-4-(chroman-6-yl)-5-(hydroxymethyl)-2-methylnicotinate

Temperature

0 °C

An ice cooled solution of Red-Al, 65 wt % solution in toluene (12.58 mL, 41.3 mmol) in tetrahydrofuran (THF) (188 mL) was treated with a solution of 3-ethyl 5-methyl 2-amino-4-(chroman-6-yl)-6-methylpyridine-3,5-dicarboxylate (7.64 g, 20.63 mmol) in tetrahydrofuran (THF) (31.4 mL) and the mixture was stirred at 0° C. for 5 minutes. The mixture was quenched with water (32 mL) then 15% NaOH (16 mL) was added. The mixture was warmed to ambient temperature and stirred for 20 minutes (solids formed). The mixture was filtered and then filtrate was concentrated. The residue was diluted with ethyl acetate, washed with brine, dried over sodium sulfate, filtered and then concentrated to afford the crude methyl 6-amino-4-(chroman-6-yl)-5-(hydroxymethyl)-2-methylnicotinate as a light brown solid which was used without further purification. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 6.87-6.72 (m, 3 H), 5.35-5.19 (m, 2 H), 4.50-4.41 (m, 2 H), 4.25-4.18 (m, 2 H), 3.50-3.45 (m, 3 H), 2.78 (t, J=6.4 Hz, 2 H), 2.38 (s, 3 H), 2.06-2.00 (m, 2 H); LC/MS (m/z) ES+=329.26 (M+1).

1. customThe mixture was quenched with water (32 mL)
2. addition15% NaOH (16 mL) was added
3. temperatureThe mixture was warmed to ambient temperature
4. stirringstirred for 20 minutes
5. custom(solids formed)
6. filtrationThe mixture was filtered
7. concentrationfiltrate was concentrated
8. additionThe residue was diluted with ethyl acetate
9. washwashed with brine
10. dry with materialdried over sodium sulfate
11. filtrationfiltered
12. concentrationconcentrated

ORD record

ord-4d4e9ef27f0f485eac318ec66e0cbb47

Source dataset

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08609653B2