1-BOC-4-(4-BROMO-BENZOYL)-PIPERIDINE

Step 1. 4-(4-Bromobenzoyl)-piperidine-1-carboxylic acid tert-butyl ester. [00596] To a 250 mL R. B. flask was charged with (4-bromophenyl)-piperidin-4- yl-methanone (5 g, 20 mmol), THF (30 mL), water (30 mL), NaStep 1 : To a solution of (4-bromophenyl)(piperidin-4-yl)methanone (600 mg, 2.23 mmol) in MeOH (5 mL) was added (Boc)To a solution of (4-bromophenyl)(piperidin-4-yl)methanone (600 mg, 2.23 mmol) in MeOH (5 mL) was added (Boc)Compound B6.1 (1.00 g; 2.721 mmol), 4-bromobenzaldehyde (0.604 g;3.266 mmol) and cesium carbonate (0.436 ml; 5.443 mmol) weresuspended in dry 1, 4-dioxane (10.0 mL) under argon atmosphere. The mixture was heated to 110 °C and stirred overnight at this temperature. The reaction mixture was cooled to room temperature, quenched with water (30 mL) and extracted with MTB-ether. The combined organic layerswere washed with 5percent citric acid solution, saturated NaHCO3 solution and brine, dried with sodium sulfate, filtered by suction and evaporated to dryness. The solid residue was triturated with petrolether/MTB-ether (1:1), filtered by suction, washed with petrolether/MTB-ether (3:1) and dried.From the filtrate further product was isolated by flash chromatography (Companion RF; 40 g Si50 silica gel column). Yield: 657 mg (66percent) colorless solid; LC/MS (A), Rt: 2.72 mm; (M+H-t-Bu) 312.0/314.0Under nitrogen atmosphere, to a stirred solution of teri-butyl 4-(4-bromobenzoyl)piperidine-l- carboxylate (100 mg; 0.26 mmol) [CAS 439811-37-7] in dichloromethane (3 mL) was added dropwise trifluoroacetic acid (0.29 mL; 3.87 mmol). The reaction solution was stirred for 0.5 hours and then concentrated to dryness to afford (4-bromophenyl)-(4-piperidyl)methanone, trifluoroacetic acid salt (100 mg) as brown solid. MS m/z (+ESI): 229.1 [M+H]+.In an autoclave, a solution of compound B6.2 (0.60 g; 1.629 mmol) and 230.8 mg (2.281 mmol) triethylamine in methanol (9 mL) and THF (20 mL)was flushed with nitrogen. (1, 1?-Bis(diphenylphosphino)- ferrocen)dichloropalladium(ll), dichloromethane (13.0 mg; 0.016 mmol) was added. Then the autoclave was filled with carbon monoxide and the mixture stirred at 70 C and a pressure of (max.) 3.7 bar for 17.5 h. The autoclave was brought to atmospheric pressure. The reaction mixture was evaporated to dryness. The crude residue was purified by flash chromatography (Companion RF; 80 g Si50 silica gel column). Yield: 0.512 g (90%) light yellow solid; LC/MS (A), Rt: 2.50 mm; (M+H-t-Bu) 274.2

Molecular Weight:368.3
XLogP3:3.6
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:4
Exact Mass:367.07831
Monoisotopic Mass:367.07831
Topological Polar Surface Area:46.6
Heavy Atom Count:22
Complexity:403
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes