Sodium Methoxide → Tert-butyl 10-(methoxymethyl)-8-pyrimidin-2-yl-11-oxa-3,8-diazaspiro[5.5]undecane-3-carboxylate

HRID 72898Notes

Reaction equation

HRID 72898 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[N:3][C:2]=1[N:7]1[CH2:12][C:11]2([CH2:17][CH2:16][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:14][CH2:13]2)[O:10][CH:9]([CH2:25][O:26]S(C2C=CC(C)=CC=2)(=O)=O)[CH2:8]1.[CH3:37][O-].[Na+]>>[CH3:37][O:26][CH2:25][CH:9]1[O:10][C:11]2([CH2:13][CH2:14][N:15]([C:18]([O:20][C:21]([CH3:23])([CH3:22])[CH3:24])=[O:19])[CH2:16][CH2:17]2)[CH2:12][N:7]([C:2]2[N:1]=[CH:6][CH:5]=[CH:4][N:3]=2)[CH2:8]1

Participants

3

Reactant 2

HCID 10942334Sodium MethoxideHCID 86672473Tert-butyl 4-(pyrimidin-2-yl)-2-(tosyloxymethyl)-1-oxa-4,9-diazaspiro[5.5]undecane-9-carboxylate

Product 1

HCID 70872731Tert-butyl 10-(methoxymethyl)-8-pyrimidin-2-yl-11-oxa-3,8-diazaspiro[5.5]undecane-3-carboxylate

Procedure

Tert-butyl 4-(pyrimidin-2-yl)-2-(tosyloxymethyl)-1-oxa-4,9-diazaspiro[5.5]undecane-9-carboxylate (1.83 g, 3.53 mmol) was dissolved in a solution of sodium methoxide (71 mL of 0.5 M in methanol, 35 mmol) and refluxed for 18 h. The solvent was evaporated to dryness and the residue dissolved in dichloromethane (200 mL). The solution was washed with water and brine, dried over Na2SO4, filtered and concentrated in vacuo. Silica gel chromatography (5-80% ethyl acetate/hexanes) provided tert-butyl 10-(methoxymethyl)-8-pyrimidin-2-yl-11-oxa-3,8-diazaspiro[5.5]undecane-3-carboxylate as colorless oil. ESI-MS m/z calc. 378.2. Found 379.3 (M+1)+; Retention time: 1.54 minutes (3 min run). 1H NMR (400 MHz, MeOD) δ 8.31 (d, J=4.8 Hz, 2H), 6.58 (t, J=4.8 Hz, 1H), 4.72-4.52 (m, 2H), 3.91 (ddd, J=10.9, 7.9, 4.9 Hz, 1H), 3.76-3.59 (m, 2H), 3.56-3.44 (m, 2H), 3.40 (s, 3H), 3.13 (t, J=11.1 Hz, 1H), 2.85-2.65 (m, 2H), 1.98 (d, J=14.6 Hz, 2H), 1.59 (dd, J=8.7, 4.5 Hz, 2H), 1.45 (s, 9H), 1.44-1.37 (m, 1H).

Workup

  1. temperaturerefluxed for 18 h
  2. customThe solvent was evaporated to dryness
  3. dissolutionthe residue dissolved in dichloromethane (200 mL)
  4. washThe solution was washed with water and brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-be0e1ebd37c648bbbb7bb8ab548cbfc7
Source dataset
uspto-grants-2014_09
Patent number
US08828996B2

Reaction notes

Loading…