Sodium borohydride → 6'-methoxy-7',8'-dimethyl-2',4'-dihydro-1'H-spiro[cyclobutane-1,3'-quinolin]-4'-ol

To a cold solution of 6′-methoxy-7′,8′-dimethyl-1′H-spiro[cyclobutane-1,3′-quinolin]-4′(2′H)-one (2 g) in a mixture of 13 mL of THF and 5 mL of CH3OH cooled in ice bath, was added NaBH4 (2.4 g). After 2 hours, the mixture was quenched with ice, evaporated to dryness to give 6′-methoxy-7′,8′-dimethyl-2′,4′-dihydro-1′H-spiro[cyclobutane-1,3′-quinolin]-4′-ol as a crude mixture (11 g). NaBH4 (3 g) was added in portions to a mixture of trifluoroacetic acid and acetic acid (25 mL, v/v:1/1) cooled in ice bath, and to this mixture was added the above obtained mixture of 6′-methoxy-7′,8′-dimethyl-2′,4′-dihydro-1′H-spiro[cyclobutane-1,3′-quinolin]-4′-ol dissolved in 10 mL of THF. After 15 min, the mixture was quenched with ice, extracted with dichloromethane, and washed with brine. The organic phase was then washed with NaOH (2 M) and brine, dried, evaporated to dryness and passed through a silica column (Hexane: EtOAc; 10:1) to give 6′-methoxy-7′,8′-dimethyl-2′,4′-dihydro-1′H-spiro[cyclobutane-1,3′-quinoline] (1.3 g) as a liquid with slightly yellow color. 1H-NMR (300 MHz, CDCl3) δ=6.44071 (s, 1H), 3.74 (s, 3H), 3.59-3.24 (s, 1H), 3.18 (s, 2H), 2.75 (s, 2H), 2.13 (s, 3H), 2.03 (s, 3H), 2.01-1.73 (m, 6H) ppm. 13C-NMR (75 MHz, CDCl3) δ=149.88, 136.21, 123.51, 131.91, 118.09, 110.83, 56.51, 51.91, 40.82, 36.09, 30.84, 15.25, 13.07, and 12.03 ppm.

1. temperaturecooled in ice bath
2. customthe mixture was quenched with ice
3. customevaporated to dryness

ORD record

ord-3b8ff8852b204d3998b5b0d3bfa1c29d

Source dataset

uspto-grants-2009_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07576094B2