Hydrochloric Acid → 2-{[(3,5-Bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amino]-methyl}-4-trifluoromethyl-phenyl-cyclobutyl-methanol

온도

-10 °C

To a solution of 2-{[(3,5-bis-trifluoromethyl-benzyl)(2-methyl-2H-tetrazol-5-yl)amino]-methyl}-4-trifluoromethyl-benzaldehyde (1.5 g; 2.9 mmol) in tetrahydrofuran (14 mL) at −10° C. was added dropwise cyclobutylmagnesium bromide (9 mL; 5.4 mmol; 0.6M solution in tetrahydrofuran). The reaction was stirred at −10° C. for 1.5 hours. To quench the reaction, at 0° C. was added aqueous 2N hydrochloric acid. Reaction extracted with ethyl acetate. The organic was washed with aqueous 2N hydrochloric acid, water and brine. It was dried sodium sulfate and concentrated under reduced pressure. The residue was purified by 40 g RediSep column (Teledyne Isco Inc., Lincoln Nebr.) (eluted with 15-70% ethyl acetate in heptane) to give 420 mg (25% yield) as a gum. MS (ES−): Calc; 567.4, Found: 612.6 (M+HCO2). 1H NMR (400 MHz, CDCl3) δ ppm 7.78 (s, 1H), 7.66 (s, 2H), 7.52 (d, J=8.30 Hz, 1H), 7.49 (d, J=8.30 Hz, 1H), 7.35 (s, 1H), 4.86 (q, J=15.77 Hz, 2H), 4.86 (s, 1H), 4.77 (q, J=15.77, 16.18 Hz, 2H), 4.20 (s, 3H), 2.68 (m, 1H), 2.05-1.96 (m, 2H), 1.93-1.76 (m, 3H), 1.70 (m, 1H).

1. customTo quench
2. customthe reaction
3. customReaction
4. extractionextracted with ethyl acetate
5. washThe organic was washed with aqueous 2N hydrochloric acid, water and brine
6. concentrationconcentrated under reduced pressure
7. customThe residue was purified by 40 g RediSep column (Teledyne Isco Inc., Lincoln Nebr.) (eluted with 15-70% ethyl acetate in heptane)
8. customto give 420 mg (25% yield) as a gum

ORD 기록

ord-6ee311477a64480297dd3b812e4ca59f

출처 데이터셋

uspto-grants-2011_04

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US07919506B2