Imidazole → HCID 123410153, compound

Participants

Reaction Steps

To a 500 mL flask was added (1R,3S,4S)-ethyl 3-fluoro-4-hydroxycyclohexane-carboxylate (17 g, 89.3 mmol, 97.9% ee), TBSCl (17.5 g, 116.1 mmol) and DCM (200 mL). Imidazole (12.1 g, 178 mmol) was added to the resultant clear solution and the reaction mixture was stirred for 16 hours. Water (100 mL) was added and the mixture was stirred for a further 10 minutes. The phases were separated and the organic layer was washed with water (100 mL) and concentrated under reduced pressure (40±5° C., 50˜250 mbar). Purification by flash chromatography on silica eluting with a mixture of heptane and ethyl acetate (100:1) gave (1R,3S,4S)-ethyl 4-((tert-butyldimethylsilyl)oxy)-3-fluorocyclohexanecarboxylate as a colorless oil (20.6 g, yield 75.7%). 1H NMR (400 MHz, DMSO-d6): 4.38˜4.52 (m, 1H), 4.03˜4.08 (dd, J=12 Hz, J=8 Hz, 2H), 3.77˜3.81 (m, 1H), 2.54˜2.60 (m, 1H), 1.93˜2.06 (m, 1H), 1.58˜1.86 (m, 4H), 1.46˜1.50 (m, 1H), 1.17˜1.20 (t, J=12 Hz, J=6 Hz, 3H), 0.85 (s, 9H), 0.03˜0.04 (d, J=4 Hz, 8H), [M+H]+=305.1 via GC-MS (Instrument: Agilent Technologies, GC 6890N, MS 5975C. GC conditions: Column: HP—5 MS, Capillary: 30.0 m×250 μm×0.25 μm, Detecor parameters: Temperature: 350° C., Flow H2: 40 mL/min, Air flow: 400 mL/min, Makeup (He): 40 mL/min. Injector parameters: temperature: 200° C. Split ratio: 100:1. Carrier gas: He, Flow: 2.0 mL/min, Mode: Constant flow. Oven parameters: 0 min, 50° C.; 2.0 min, 50° C.; 5.33 min, 100° C.; 15.83 min, 270° C. Injection volume: 1 μL, Syringe wash solvent: acetonitrile. MS conditions: Volt: 70 EV, Scan range: m/z=50˜550)

Provenance & Evidence