Hexane → (1R,3S,6S)-2-(tert-butoxycarbonyl)-2-azabicyclo[4.1.0]heptane-3-carboxylic acid

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Reaction Steps

To a solution of sodium periodate (15.5 g, 72.6 mmol) in water (80 mL) was added a solution of (1R,3S,6S)-tert-butyl 3-(hydroxymethyl)-2-azabicyclo[4.1.0]heptane-2-carboxylate (5.5 g, 24.2 mmol) in ACN (60 mL) and carbon tetrachloride (60 mL). Ruthenium (III)chloride (246 mg, 1.21 mmol) was added immediately and the reaction mixture was stirred vigorously for 75 min at RT, diluted with water (80 mL), filtered, and extracted with DCM (3×100 mL). The combined organic phase was washed with brine, dried over Na2SO4, and concentrated under vacuum to provide crude product (4.75 g) as a light charcoal-color solid. The crude product was dissolved in EtOAc (20 mL) with heating and allowed to stand at RT with seeding. After about 15 min, rapid crystal formation was observed. About 1 h later, hexane (10 mL) was added and the mixture was refrigerated overnight, filtered, washed with 2:1 ice-water-cooled hexanes:EtOAc (50 mL) and dried under high vacuum to provide the title intermediate (1.9 g) ([a]D=−135.2) The mother liquid was re-crystallized to provide additional product (300 mg) ([a]D=−142.6). 1H NMR: (DMSO-d6, 400 MHz) δ (ppm) 4.1 (m, 1H), 2.60 (m, 1H), 1.70 (m, 1H), 1.30 (m, 3H), 1.17 (m, 9H), 0.96 (m, 1H), 0.50 (m, 1H), 0.0 (m, 1H)

Provenance & Evidence