Hydrochloric Acid → t-Butyl N-(1-[2-chloro-9,10-dihydro-9,10-methanoanthracen-9-ylmethyl]-4-piperidyl)carbamate

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Reaction Steps

To a stirred suspension of 2-chloro-9-formyl-9,10-dihydro-9,10-methanoanthracene (3.64 g, 14.25 mmol, described in Example 107i), 4-t-butoxycarbonylaminopiperidine (3.57 g, 17.81 mmol), and activated 3A sieves (powderized, 3.64 g) in methanol (50 mL, sieve dried) was added methanolic hydrochloric acid (ca. 3.5 mL) until the pH was 7.50. After 2 h, the mixture was treated with sodium cyanoborohydride (895 mg, 14.25 mmol) in four portions over a 4 h period. After stirring the resulting mixture an additional 72 h, ethyl acetate (100 mL) and 3N sodium hydroxide (100 mL) and filtered through celite. The filtrate was treated with 3N sodium hydroxide (250 mL) and extracted with ethyl acetate (2×300 mL). The combined extracts was dried (sodium sulfate), filtered and concentrated to give a tan foam. Chromatography of this material over silica gel (eluting in sequence with 1) 90:10 acetone:hexane (6 L) and 2) 85:15 acetone:hexane (1 L)) to give the title compound as a white foam (3.24 g, 52%), mp 76.5°-80.0° C.; MS(CI): 439 (M+H); NMR (300 MHz,DMSO-d6): 1.37(m, 11H), 1.64(m, 2H), 2.21(m, 2H), 2.46(s, 2H), 2.92(m, 2H), 3.17-3.42(br m, part. submerged by H2O, 3H), 4.33(s, 1H), 6.72(m, 1H), 6.95(m, 3H), 7.19(m, 2H), 7.26(m, 2H).

Provenance & Evidence