(R)-tert-butyl 4-((5-((tert-butyldiphenylsilyl)oxy)hexyl)oxy)-4-(iodomethyl)piperidine-1-carboxylate → (R)-tert-butyl 4-((5-((tert-butyldiphenylsilyl)oxy)hexyl)oxy)-4-methylpiperidine-1-carboxylate

HRID 921161Notes

Reaction equation

HRID 921161 reaction equation
[Si:1]([O:18][C@H:19]([CH3:40])[CH2:20][CH2:21][CH2:22][CH2:23][O:24][C:25]1([CH2:38]I)[CH2:30][CH2:29][N:28]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:27][CH2:26]1)([C:14]([CH3:17])([CH3:16])[CH3:15])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1>CO.[Pd]>[Si:1]([O:18][C@H:19]([CH3:40])[CH2:20][CH2:21][CH2:22][CH2:23][O:24][C:25]1([CH3:38])[CH2:30][CH2:29][N:28]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:27][CH2:26]1)([C:14]([CH3:16])([CH3:17])[CH3:15])([C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 1

HCID 123897146(R)-tert-butyl 4-((5-((tert-butyldiphenylsilyl)oxy)hexyl)oxy)-4-(iodomethyl)piperidine-1-carboxylate

Product 1

HCID 123285187(R)-tert-butyl 4-((5-((tert-butyldiphenylsilyl)oxy)hexyl)oxy)-4-methylpiperidine-1-carboxylateYield 77.5%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

To a solution of (R)-tert-butyl 4-((5-((tert-butyldiphenylsilyl)oxy)hexyl)oxy)-4-(iodomethyl)piperidine-1-carboxylate (13 g, 19.12 mmol) in MeOH (100 mL) was added TEA (5.33 mL, 38.2 mmol) followed by 10% Pd—C (1.018 g, 0.956 mmol) and the resulting mixture was subjected to hydrogenolysis under PAR at 50 PSI. After 16 h, mixture was filtered through a pad of celite and the filtrate was concentrated. The residue was then purified by Biotage (0-15% EtOAc/hexane) to afford (R)-tert-butyl 4-((5-((tert-butyldiphenylsilyl)oxy)hexyl)oxy)-4-methylpiperidine-1-carboxylate (8.2 g, 14.81 mmol, 77% yield) as light yellow oil. 1H NMR (500 MHz, CDCl3) δ 7.73-7.67 (m, 4H), 7.48-7.35 (m, 6H), 3.86 (sxt, J=5.8 Hz, 1H), 3.72 (br. s., 2H), 3.24 (t, J=6.3 Hz, 2H), 3.10 (br. s., 2H), 1.78-1.66 (m, 3H), 1.59-1.51 (m, 1H), 1.50-1.47 (m, 6H), 1.47 (s, 9H), 1.14 (s, 3H), 1.10-1.03 (m, 12H). LCMS (M+Na)=576.7.

Workup

  1. filtrationmixture was filtered through a pad of celite
  2. concentrationthe filtrate was concentrated
  3. customThe residue was then purified by Biotage (0-15% EtOAc/hexane)

Sources & evidence

ORD record
ord-bc89e82c557e4052bd8d788448df382f
Source dataset
uspto-grants-2016_03
Patent number
US09273067B2

Reaction notes

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