Methyl iodide → Tert-butyl 8-tert-butyl-10-(methoxymethyl)-11-oxa-3,8-diazaspiro[5.5]undecane-3-carboxylate

HRID 72916Notes

Reaction equation

HRID 72916 reaction equation
[C:1]([N:5]1[CH2:22][CH:21]([CH2:23][OH:24])[O:20][C:7]2([CH2:12][CH2:11][N:10]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:9][CH2:8]2)[CH2:6]1)([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[CH3:27]I>CN(C)C=O>[C:1]([N:5]1[CH2:22][CH:21]([CH2:23][O:24][CH3:27])[O:20][C:7]2([CH2:12][CH2:11][N:10]([C:13]([O:15][C:16]([CH3:17])([CH3:18])[CH3:19])=[O:14])[CH2:9][CH2:8]2)[CH2:6]1)([CH3:2])([CH3:3])[CH3:4]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 70872649Tert-butyl 8-tert-butyl-10-(hydroxymethyl)-11-oxa-3,8-diazaspiro[5.5]undecane-3-carboxylate

Product 1

HCID 70872449Tert-butyl 8-tert-butyl-10-(methoxymethyl)-11-oxa-3,8-diazaspiro[5.5]undecane-3-carboxylateYield 98%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of tert-butyl 8-tert-butyl-10-(hydroxymethyl)-11-oxa-3,8-diazaspiro[5.5]undecane-3-carboxylate (720 mg, 2.10 mmol) in N,N-dimethylformamide (7.0 mL) was added sodium hydride (588 mg, 14.7 mmol) and the reaction stirred for 10 min. Methyl iodide (916 μL, 14.7 mmol) was added and the reaction mixture stirred for 20 min. The reaction was quenched with saturated aqueous NH4Cl and extracted with ethyl acetate (2×25 mL). The combined organic layers were dried over Na2SO4, filtered and concentrated to provide tert-butyl 8-tert-butyl-10-(methoxymethyl)-11-oxa-3,8-diazaspiro[5.5]undecane-3-carboxylate (732 mg, 2.05 mmol, 98%). ESI-MS m/z calc. 356.3. Found 357.3 (M+1)+; Retention time: 0.97 minutes (3 min run).

Workup

  1. stirringthe reaction mixture stirred for 20 min
  2. customThe reaction was quenched with saturated aqueous NH4Cl
  3. extractionextracted with ethyl acetate (2×25 mL)
  4. dry with materialThe combined organic layers were dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-8bf7641db4344e5eba92b06e83a8c893
Source dataset
uspto-grants-2014_09
Patent number
US08828996B2

Reaction notes

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