Imidazole → Benzenamine, 2-[[[(1,1-dimethylethyl)dimethylsilyl]oxy]methyl]-

Participants

Reaction Steps

A mixture of 3.0 g (20 mmol) of 3-aminobenzyl alcohol, 3.36 g (22.0 mmol) of t-butyldimethylsilyl chloride and 1.52 g (22.0 mmol) of imidazole were dissolved in 20 mL of DMF. The solution was stirred at rt for 16 h and then diluted with 250 mL of hexane and 250 mL of EtOAc. The organic phase was washed twice with brine, dried over MgSO4 and concentrated to give 4.8 g of 3-([t-butyldimethylsilyloxy]methyl-benzenamine as a clear oil. This was dissolved in 100 mL of CH2Cl2, cooled with stirring to −65° C. and 2.17 g (20.0 mmol) of t-butyl hypochlorite was added. After 10 min of stirring, a solution of 2.68 g (20.0 mmol) of ethyl methylthioaceatate in 10 mL of CH2Cl2 was added, and the solution was stirred for 1 h. TEA (2.02 g, 20.0 mmol) was added and the reaction was warmed to rt over 1 h. The solution was washed with water and concentrated to an oil. This was redissolved in 100 mL of ether, 12 mL of 2 N hydrochloric acid was added, and the mixture was stirred overnight. The ether phase was separated and concentrated to an oil. This was chromatographed on silica gel eluting with hexane:EtOAc (initially a 3:1 ratio increasing to 1:2) to yield 0.82 g (20%) of 4-hydroxymethyl-3-methylsulfanyl-1,3-dihydro-indol-2-one: 1H NMR (DMSO-d6): δ1.89 (s, 3H), 4.45 (s, 1H), 4.62 (m, 2H), 5.1 (bs, 1H), 6.87 (d, J=7.7 Hz, 1H), 7.02 (d, J=7.7 Hz, 1H), 7.17 (t, J=7.7 Hz, 1H), 10.44 (s, 1H). Further elution yielded 0.53 g (13%) of 6-hydroxymethyl-3-methysulfanyl-1,3-dihydro-indol-2-one: 1H NMR (DMSO-d6): δ1.99 (s, 3H), 4.48 (s, 2H), 4.50 (s, 1H), 5.1 (bs, 1H), 6.84 (s, 1H), 6.94 (d, J=7.6 Hz, 1H), 7.22 (d, J=7.6 Hz, 1H), 10.54 (s, 1H).

Provenance & Evidence