2,2-dimethyl-3-phenylpropan-1-ol

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of oxalyl chloride (10.1 g, 79.4 mmol) in methylene chloride (70 mL) at −78° C. was added dimethylsulfoxide (10.0 mL, 139 mmol). The solution was stirred at −78° C. for 10 minutes then a solution of 2,2-dimethyl-3-phenylpropanol (6.52 g, 39.7 mmol) in methylene chloride (15 mL) was added. After stirring the reaction at −78° C. for 30 minutes, triethylamine (20.1 g, 198 mmol) was added and the reaction mixture was stirred for 10 minutes, then at 0° C. for 5 minutes. The reaction mixture was quenched with saturated aqueous ammonium chloride (20 mL) and the aqueous layer was extracted with diethyl ether (2×50 mL). The organic portions were individually washed with brine (15 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was redissolved in diethyl ether and the resulting precipitate was filtered through a pad of Celite. The filtrate was concentrated under reduced pressure to provide the title compound (6.89 g) as an oil. After stirring the reaction at −78° C. for 30 minutes the reaction mixture was stirred for 10 minutes at 0° C. for 5 minutes The reaction mixture was quenched with saturated aqueous ammonium chloride (20 mL) the aqueous layer was extracted with diethyl ether (2×50 mL) The organic portions were individually washed with brine (15 mL) dried over anhydrous sodium sulfate concentrated under reduced pressure The residue was redissolved in diethyl ether the resulting precipitate was filtered through a pad of Celite The filtrate was concentrated under reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound was prepared from 5-{2 -[2-(3-chloro-phenyl)-2-hydroxy-ethylamino]-propyl}-benzo[1,3]dioxole-2,2-dicarboxylic acid and 2,2-dimethyl-3-phenylpropanol according to the procedure of Example 1 as an off-white solid; 1H NMR (DMSO-d6,400 MHz) δ 0.82 (s, 12H, 4×CH3), 1.08 (d, J=6.37 Hz, 3H, CH3), 2.6 (m, 1H, CH), 3-3.3 (m, 3H, CH, CH2), 3.4 (brs, 1H, CH), 3.96 (s, 4H, OCH2, OCH2), 5.04 (m, 1H, CH), 6.35 (d, J=4.17 Hz, 1H, OH), 6.89 (dd, J=8.13, 1.53 Hz, 1H, Ar--H), 7.05 (m, 4H, Ar--H), 7.14 (m, 8H, Ar--H), 7.38-7.42 (m, 3H, Ar--H), 7.5 (s, 1H, Ar--H), 8.81 (brs, 1H, NH), 9.38 (brs, 1H, NH); IR (KBr, cm-) 3400 (OH), 2900 (NH), 1760 (CO); MS m/e 714 (M+H)+ ; Analysis for: C42H48ClNO7 ×HCl: Calc'd: C, 67.19; H, 6.58; N, 1.87; Found: C, 66.69; H, 6.53; N, 1.83.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 354 g 2,2-dimethyl-3-phenyl-propanal (1a) was hydrogenated in an autoclave with 2 g copper chromite (G-79) at 150° C. and 120 bar until it had absorbed 1 equivalent of hydrogen. When the pressure had been released in the autoclave the catalyst was separated off. Distillation on a 60 cm packed column yielded 320 g (90%) 2,2-dimethyl-3-phenyl-propanal (1b) in the form of a colourless, viscous oil. bp (2 mm)=90° C., mp. 34°-36° C. --NMR (CCl4): δ-0.88, s, 6H (2,2--CH3), 2.55, s (CH2 --3), 3.37, s (CH2 --1), 7.1-7.3, br.s (phenyl--H). --IR: 3400 cm-1 (O--H). --MS: m/e (%)=164 (16, M+), 133 (5), 131 (4), 117 (6), 115 (8), 105 (4), 92 (100), 91 (83). C11H16O (164.2). was separated off Distillation on a 60 cm