Methyl iodide → 1-Boc-3,4,4-trimethoxypiperidine

HRID 2168194Notes

Reaction equation

HRID 2168194 reaction equation
[OH:1][CH:2]1[C:7]([O:10][CH3:11])([O:8][CH3:9])[CH2:6][CH2:5][N:4]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:3]1.[CH3:19]C(C)([O-])C.[K+].CI>C1COCC1>[CH3:19][O:1][CH:2]1[C:7]([O:8][CH3:9])([O:10][CH3:11])[CH2:6][CH2:5][N:4]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:3]1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 11425480Tert-butyl 3-hydroxy-4,4-dimethoxypiperidine-1-carboxylateHCID 23665647Potassium tert-butoxide

Product 1

HCID 592630891-Boc-3,4,4-trimethoxypiperidine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 1,1-dimethylethyl 3-hydroxy-4,4-bis(methyloxy)-1-piperidinecarboxylate D16 (11 g) in THF (150 ml) was added Potassium t-Butoxide (23.5 g, 210 mmol) at 0° C. The reaction mixture was stirred for 20 mins and the methyliodide (5.2 ml, 84 mmol) was added. The reaction mixture was allowed to warm up to room temperature and stirred overnight. The resulting mixture was concentrated and dissolved in EtOAc and washed with water. The organic layer was concentrated in vacuo to obtain crude product. Product was purified on silica gel eluting with DCM/MeOH 50/1 to obtain the desired product D17 as a yellow oil in 5 g. LCMS [MH+] [email protected] min (5 min run)

Workup

  1. stirringstirred overnight
  2. concentrationThe resulting mixture was concentrated
  3. dissolutiondissolved in EtOAc
  4. washwashed with water
  5. concentrationThe organic layer was concentrated in vacuo
  6. customto obtain crude product
  7. customProduct was purified on silica gel eluting with DCM/MeOH 50/1

Sources & evidence

ORD record
ord-648aa14ff4da4d168dbc693d25cf26db
Source dataset
uspto-grants-2015_06
Patent number
US09045485B2

Reaction notes

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