Diisopropylamine → 2-[(R)-5-(4-Carbamoyl-phenyl)-indan-1-yl]-2,7-diazaspiro[3.5]nonane-7-carboxylic acid tert-butyl ester

Participants

Reaction Conditions

Reaction Steps

2-((R)-5-Bromo-indan-1-yl)-2,7-diaza-spiro[3.5]nonane-7-carboxylic acid tert-butyl ester (3-1a, 500 mg, 1.19 mmol), 4-carbamoylphenylboronic acid (587 mg, 3.56 mmol), Pd(OAc)2 (14 mg, 0.06 mmol) and TPPTS ligand (3,3′,3″-phosphinidynetris[benzenesulfonic acid]trisodium salt, 135 mg, 0.24 mmol) were suspended in 10 mL water and 5 mL acetonitrile. Diisopropylamine (291 mg, 2.85 mmol) was added, and the mixture was heated to 90° C. for 2 hours. The mixture was cooled to room temperature and was diluted with ethyl acetate (150 mL). The organic solution was washed with water (50 mL), dried (MgSO4), filtered through Celite® and concentrated to give 499 mg (91%) of the title compound as a light pink powder. MS (ES+) 462.1 (M+H)+. 1H NMR (CD3OD) δ 1.42 (s, 9H), 1.64-1.74 (m, 4H), 1.83-1.96 (m, 1H), 2.17-2.30 (m, 1H), 2.80-2.93 (m, 1H), 3.10 (dt, 1H), 3.24-3.28 (m, 2H), 3.31-3.38 (m, 6H), 4.06 (dd, 1H), 6.79 (d, 1H), 7.39-7.49 (m, 2H), 7.53 (s, 1H), 7.67 (d, 2H), 7.73 (d, 1H), 7.89-7.94 (m, 2H).

Provenance & Evidence