(3,3-Difluorocyclobutyl)methanol

Step 1(3, 3-difluorocyclobutyl)methanolA suspension of sodium borohydride (0.556 g, 14.70 mmol) in tetrahydrofuran (50 mL) was cooled to 0 °C and then treated dropwise with a solution of 3, 3- difluorocyclobutanecarboxylic acid (2 g, 14.70 mmol) in tetrahydrofuran (50 mL). Aftercompletion of the addition, the reaction flask was removed from the cold bath, and the reaction was stirred at room temperature for 1 hour. After this time, the reaction mixture was cooled again to 0 °C. Then boron trifluoride-diethyl etherate (1.862 mL, 14.70 mmol) was added slowly, and the reaction was allowed to stir overnight at 0 °C with gradual warming to room temperature. The mixture was then again cooled to 0 °C and quenched with 25 mL of 95percent ethanol. The mixture was stirred for 1 hour in the ice bath, and then the mixture was concentrated in vacuo. The residue was partitioned between CH2C12 and brine, and the phases were separated. The organic layer was dried over Na2SO4 and concentrated in vacuo to afford the titled compound as a pale tan oil, 1.629 g (9 1percent). ‘H NMR (300 MHz, CDC13) ppm 2.3 1-2.38 (m, 3H), 2.60-2.66 (m, 2H), 3.67 (m, 2H); MS (DCI) m/z 123 (M+H).Step 1 Preparation 36(3, 3-Difluorocvclobutyl)methanol3, 3-Difluorocyclobutanecarboxylic acid (5.0 g, 36.7 mmol) was dissolved in THF (50.0 mL) and the reaction was cooled to 03, 3-Difluorocyclobutanecarboxylic acid (5.0 g, 36.7 mmol) was dissolved in THF (50.0 mL) and the reaction was cooled to 0° C. under nitrogen with an ice bath. Then thiodimethane-borane (1:1) (5.23 mL, 61.4 mmol) was added drop wise and the mixture stirred at 0° C. for 4 hours. An aqueous solution of HCl (1.0 M, 75 mL) and EtOAc (100 mL) were added and the organic layer was then collected and further washed with water (30 mL). The organic layer was then dried over sodium sulfate, filtered, and concentrated in vacuo to afford title compound (3.25 g, 73percent):Example 19A To a mixture of 3, 3-difluorocyclobutanecarboxylic acid (970 mg) in TifF (25 mL) cooled at 0°C was added dropwise borane-methyl sulfide complex (1.354 mL) under N2. The mixture was stirred for 4 hours at 0°C. The mixture was quenched with the conc. HC1 solution. The aqueous layer wasextracted with DCM (2x30 mL). The combined organic layers were dried over Na2SO4 and filtered.The residue was concentrated in vacuo to afford the title compound (650 mg) as colorless oil. ‘HNMR (400 MHz, CDC13): 3.62 (d, J= 5.2 Hz, 2H), 2.75 (brs, 1 H), 2.62-2.54 (m, 2H), 2.35-2.25(m, 3H).Description 10(3, 3-Difluorocyclobutyl)methanol (PlO)F—7LTTo the mixture of 3, 3-difluorocyclobutanecarboxylic acid (1 g) in THF (20 mL) was added borane(1 M in THF, 29.4 mL) during 30 mm. The reaction mixture was stirred at 20°C for 6 hours, then concentrated under vacuum to afford the title compound (1 g) as white solid. 1H NMR (500 MHz, CDC13): 3.72-3.70 (m, 2H), 2.68-2.62 (m, 2H), 2.40-2.33 (m, 3H).A solution of the compound described in Preparation 42 (2.30 g, 14 mmol), in diethyl ether (14 ml_), was added to a suspension of lithium aluminium hydride (1.17 g, 30.8 mmol), in diethyl ether (70 ml_), cooled to -45 Example 37fStep 1. (3, 3-difluorocyclobutyl)methyl 4-methylbenzenesulfonate (53-2) To a solution of

Molecular Weight:122.11
XLogP3:1
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:122.05432120
Monoisotopic Mass:122.05432120
Topological Polar Surface Area:20.2
Heavy Atom Count:8
Complexity:84.4
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes