Cl.[F:2][C:3]1([F:8])[CH2:7][CH2:6][NH:5][CH2:4]1.[CH:9]([CH:11]1[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH2:12]1)=O.CCN(C(C)C)C(C)C.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>ClCCCl>[F:2][C:3]1([F:8])[CH2:7][CH2:6][N:5]([CH2:9][CH:11]2[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:21])([CH3:23])[CH3:22])=[O:18])[CH2:13][CH2:12]2)[CH2:4]1A mixture of 3,3-difluoropyrrolidine hydrochloride (965 mg, 6.722 mmol), tert-butyl 4-formylpiperidine-1-carboxylate (1.720 g, 8.066 mmol), DIPEA (955.6 mg, 1.288 mL, 7.394 mmol) and crushed 4A MS (965 mg) in DCE (30 mL) were stirred at ambient temperature for 3 hours. NaBH(OAc)3 (2.848 g, 13.44 mmol) was added and the reaction stirred at ambient temperature for a further 16 hours. The mixture was filter through Celite (washing with DCM) and the filtrate concentrated in vacuo. The residue was purified by column chromatography (ISCO Companion, 80 g column, eluting with 0 to 10% MeOH/DCM, loaded in DCM) to give the sub-title product as a colourless oil that was used directly into next step without further purification. LC-MS ES+: 305.1.
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