Methyl iodide → tert-Butyl 4-(methoxymethyl)piperidine-1-carboxylate

HRID 341509Notes

Reaction equation

HRID 341509 reaction equation
[OH:1][CH2:2][CH:3]1[CH2:8][CH2:7][N:6]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:5][CH2:4]1.[H-].[Na+].I[CH3:19]>CN(C=O)C>[CH3:19][O:1][CH2:2][CH:3]1[CH2:8][CH2:7][N:6]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:5][CH2:4]1

Participants

5

Reactant 3

HCID 6328Methyl iodide2×HCID 24758Sodium hydride2×HCID 2764081Tert-butyl 4-(hydroxymethyl)piperidine-1-carboxylate

Product 1

HCID 21989877tert-Butyl 4-(methoxymethyl)piperidine-1-carboxylateYield 23.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A solution of tert-butyl 4-(hydroxymethyl)piperidine-1-carboxylate (0.300 g, 1.395 mmol) in DMF (2.5 mL) was added dropwise to a suspension of sodium hydride (60% dispersion in mineral oil, 0.067 g, 1.674 mmol) in anhydrous DMF (2.5 mL) at 0 C. The reaction mixture was stirred at 0 C for 10 min followed by dropwise addition of iodomethane (86 μL, 1.395 mmol). The mixture was warmed to room temperature and stirred for 18 h. The reaction mixture was re-treated with sodium hydride (60% dispersion in mineral oil, 0.067 g, 1.674 mmol) and iodomethane (86 μL, 1.395 mmol) and was stirred at room temperature for 18 h. The reaction mixture was evaporated under reduced pressure, dissolved in DCM and washed with a saturated aqueous solution of sodium bicarbonate. The organic extracts were combined, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The crude material was purified by FCC (EtOAc: heptane, 1:1) to afford the title compound (0.074 g, 23%). Method B HPLC-MS: MH+ requires m/z=229 Found: m/z=174 (MH+-tBu) Rt=1.98 min (99%).

Workup

  1. stirringstirred for 18 h
  2. stirringwas stirred at room temperature for 18 h
  3. customThe reaction mixture was evaporated under reduced pressure
  4. dissolutiondissolved in DCM
  5. washwashed with a saturated aqueous solution of sodium bicarbonate
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe crude material was purified by FCC (EtOAc: heptane, 1:1)

Sources & evidence

ORD record
ord-a6aac4fafd634fe2978a54e13ff0eafc
Source dataset
uspto-grants-2014_11
Patent number
US08895733B2

Reaction notes

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