[C:1]([O:5][C:6](=[O:14])[N:7]([CH2:11][CH2:12]Cl)[CH2:8][CH2:9]Cl)([CH3:4])([CH3:3])[CH3:2].[Br:15][C:16]1[CH:21]=[CH:20][C:19]([CH2:22][C:23]#[N:24])=[CH:18][CH:17]=1.[OH-].[Na+]>C1(C)C=CC=CC=1.O.[Br-].C([P+](CCCC)(CCCC)CCCC)CCCCCCCCCCCCCCC>[C:1]([O:5][C:6]([N:7]1[CH2:11][CH2:12][C:22]([C:19]2[CH:20]=[CH:21][C:16]([Br:15])=[CH:17][CH:18]=2)([C:23]#[N:24])[CH2:9][CH2:8]1)=[O:14])([CH3:4])([CH3:3])[CH3:2]To a mixture of bis-(2-chloro-ethyl)-carbamic acid tert-butyl ester from Step 1 (7.26 g, 30 mmol, 1 eq) and 4-bromophenylacetonitrile (5.88 g, 30 mmol, 1 eq) in 38 mL of toluene and 76 mL of H2O was added NaOH (45.6 g, 114 mmol, 10M solution) followed by hexadecyltributylphosphonium bromide (3.0 g, 6.0 mmol, 0.2 eq). The resulting dark mixture was heated to 110° C. for 2 h and then allowed to cool to ambient temperature. It was extracted with three 200 mL portions of ethyl acetate and the combined organic extracts were dried over Na2SO4, filtered and concentrated by rotary evaporation to give the crude product as a black oily residue. Purification by flash column chromatography eluting with a gradient of 5-10% ethyl acetate in hexane gave 5.67 g of 4-(4-bromo-phenyl)-4-cyano-piperidine-1-carboxylic acid tert-butyl ester as a pale yellow foam. 1H NMR (300 MHz, CDCl3): δ 7.56-7.48 (d, 2H), 7.36-7.30(d, 2H), 4.40-4.10 (br. s, 2H), 3.27-3.05 (t, 2H), 2.10-1.80 (m, 4H), 1.45 (s, 9H).
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