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

HRID 921160Notes

Reaction equation

HRID 921160 reaction equation
[Si:1]([O:18][C@H:19]([CH3:25])[CH2:20][CH2:21][CH2:22][CH2:23][OH:24])([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.[CH2:26]=[C:27]1[CH2:32][CH2:31][N:30]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:29][CH2:28]1.[Si](OS(C(F)(F)F)(=O)=O)(C)(C)C.[I:52]N1C(=O)CCC1=O.[O-]S([O-])(=S)=O.[Na+].[Na+]>C(Cl)Cl.[O-]S([O-])(=O)=O.[Cu+2].CCOCC>[Si:1]([O:18][C@H:19]([CH3:25])[CH2:20][CH2:21][CH2:22][CH2:23][O:24][C:27]1([CH2:26][I:52])[CH2:32][CH2:31][N:30]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:29][CH2:28]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

9

Reactant 5

HCID 24477Sodium ThiosulfateHCID 65367Trimethylsilyl triflateHCID 120273N-IodosuccinimideHCID 27568081-Boc-4-MethylenepiperidineHCID 15953234(R)-5-((tert-butyldiphenylsilyl)oxy)hexan-1-ol

Product 1

HCID 123897146(R)-tert-butyl 4-((5-((tert-butyldiphenylsilyl)oxy)hexyl)oxy)-4-(iodomethyl)piperidine-1-carboxylateYield 66.3%

Reagents, catalysts & solvents 3

HCID 24462Copper SulfateCatalystHCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
2.5 °C

Procedure

To a solution of (R)-5-((tert-butyldiphenylsilyl)oxy)hexan-1-ol (8.23 g, 23.08 mmol) and tert-butyl 4-methylenepiperidine-1-carboxylate (6.83 g, 34.6 mmol) in CH2Cl2 (40 mL) was added TMS-OTf (0.334 mL, 1.846 mmol), followed by CuSO4 (1.842 g, 11.54 mmol) and the slurry was cooled to 0-5° C. N-iodosuccinimide (7.79 g, 34.6 mmol) was then added in one portion and the slurry was stirred for 0-5° C. for additional 16 h, then warmed to room temp over 2-3 h. Ether (200 mL) followed by aqueous solution of Na2S2O3 (5% 100 mL) was added and the layers were separated. Organic layer was then washed with water (100 mL), dried (Na2SO4), filtered and concentrated. The residue was then purified by column chromatography (EtOAc/hexanes, 5-20%) to afford (R)-tert-butyl 4-((5-((tert-butyldiphenylsilyl)oxy)hexyl)oxy)-4-(iodomethyl)piperidine-1-carboxylate (13 g, 15.30 mmol, 66.3% yield) as yellow oil. 1H NMR (500 MHz, CDCl3) δ 7.70 (dt, J=7.1, 1.7 Hz, 4H), 7.47-7.36 (m, 6H), 3.93 (s, 1H), 3.91-3.69 (m, 2H), 3.25 (br. s., 2H), 3.20 (t, J=6.4 Hz, 2H), 3.00 (br. s., 2H), 1.87 (d, J=13.1 Hz, 2H), 1.57-1.50 (m, 4H), 1.48 (s, 9H), 1.45-1.35 (m, 4H), 1.15-1.02 (m, 12H). LCMS (M-BOc)=580.6.

Workup

  1. temperaturewarmed to room temp over 2-3 h
  2. additionwas added
  3. customthe layers were separated
  4. washOrganic layer was then washed with water (100 mL)
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was then purified by column chromatography (EtOAc/hexanes, 5-20%)

Sources & evidence

ORD record
ord-d7010088d2354cd498111753846c8441
Source dataset
uspto-grants-2016_03
Patent number
US09273067B2

Reaction notes

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