18-Crown-6 → HCID 131724532, compound

Temperature

-78 °C

To a solution of 18-crown-6 (7.6 g, 28.7 mmol) in 100 mL of tetrahydrofuran at −78° C. was added bis(2,2,2-trifluoroethyl) (methoxycarbonylmethyl)phosphonate (2.0 g, 6.31 mmol). Potassium bis(trimethylsilyl)amide (12.6 mL of a 0.5M solution in toluene, 6.31 mmol) was added dropwise over 15 min and the mixture was stirred an additional 30 min at −78° C. Then there was added tert-butyl 8-formyl-3,4-dihydro-1(2H)-quinolinecarboxylate from EXAMPLE 1, Part B (1.5 g, 5.74 mmol) in 10 mL of tetrahydrofuran and the resulting cloudy mixture was stirred −78° C. for 1 h. The reaction was quenched with saturated aqueous ammonium chloride, diluted with ethyl acetate, washed with brine, dried (MgSO4), filtered through a pad of silica gel and concentrated in vacuo. The residue was purified by flash chromatography (elution with 6:1 hexane/ethyl acetate) to afford 1.7 g (93%) of the title compound as a solid. 1H NMR (CDCl3): δ 7.42-7.36 (m, 1H), 7.12-7.08 (m, 2H), 7.02 (d, 1H, J=12.4 Hz), 5.89 (d, 1H, J=12.0 Hz), 4.37-4.22 (broad m, 1H), 4.14 (q, 2H, J=7.3 Hz), 3.10-2.98 (broad s, 1H), 2.79-2.70 (m, 2H), 2.18-2.05 (broad m, 1H), 1.95-1.88 (broad s, 1H), 1.42 (broad s, 9H), 1.28 (t, 3H, J=7.2 Hz).

1. stirringthe resulting cloudy mixture was stirred −78° C. for 1 h
2. customThe reaction was quenched with saturated aqueous ammonium chloride
3. additiondiluted with ethyl acetate
4. washwashed with brine
5. dry with materialdried (MgSO4)
6. filtrationfiltered through a pad of silica gel
7. concentrationconcentrated in vacuo
8. customThe residue was purified by flash chromatography (elution with 6:1 hexane/ethyl acetate)

ORD record

ord-4d7fc76332d24f3cafaad84ee0a0de46

Source dataset

uspto-grants-2004_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06777406B2