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

HRID 72896Notes

Reaction equation

HRID 72896 reaction equation
[OH:1][CH2:2][CH:3]1[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][NH:5][CH2:4]1.Cl[C:22]1[N:27]=[CH:26][CH:25]=[CH:24][N:23]=1.C(=O)([O-])[O-].[Na+].[Na+].C(OCC)(=O)C.CCCCCC>CS(C)=O.C(OCC)(=O)C>[OH:1][CH2:2][CH:3]1[O:20][C:7]2([CH2:8][CH2:9][N:10]([C:13]([O:15][C:16]([CH3:17])([CH3:19])[CH3:18])=[O:14])[CH2:11][CH2:12]2)[CH2:6][N:5]([C:22]2[N:27]=[CH:26][CH:25]=[CH:24][N:23]=2)[CH2:4]1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 744042-ChloropyrimidineHCID 21226206Ethyl acetate hexaneHCID 70872648Tert-butyl 10-(hydroxymethyl)-11-oxa-3,8-diazaspiro[5.5]undecane-3-carboxylate

Product 1

HCID 70872753Tert-butyl 10-(hydroxymethyl)-8-pyrimidin-2-yl-11-oxa-3,8-diazaspiro[5.5]undecane-3-carboxylateYield 80.8%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of tert-butyl 10-(hydroxymethyl)-11-oxa-3,8-diazaspiro[5.5]undecane-3-carboxylate (3.10 g, 10.8 mmol), 2-chloropyrimidine (1.86 g, 16.2 mmol) and sodium carbonate (2.30 g, 21.7 mmol) in DMSO (15 mL) was heated at 110° C. for 1 h. The reaction mixture was diluted with ethyl acetate (200 mL), washed with water (4×100 mL), dried over Na2SO4, and concentrated in vacuo. Silica gel column chromatography (0-60% ethyl acetate/hexane) provided tert-butyl 10-(hydroxymethyl)-8-pyrimidin-2-yl-11-oxa-3,8-diazaspiro[5.5]undecane-3-carboxylate (3.18 g, 8.73 mmol, 80%). ESI-MS m/z calc. 364.2. Found 365.3 (M+1)+; Retention time: 1.21 minutes (3 min run). 1H NMR (400 MHz, CDCl3) δ 8.29 (d, J=4.7 Hz, 2H), 6.50 (t, J=4.7 Hz, 1H), 4.64 (ddd, J=16.0, 8.5, 1.5 Hz, 2H), 3.90-3.80 (m, 1H), 3.79-3.56 (m, 4H), 3.44-3.22 (m, 1H), 3.13 (t, J=10.6 Hz, 1H), 2.90-2.71 (m, 2H), 2.19 (d, J=8.9 Hz, 1H), 1.98 (dd, J=10.6, 3.6 Hz, 1H), 1.69-1.58 (m, 2H), 1.45 (s, 9H).

Workup

  1. washwashed with water (4×100 mL)
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-fda9abb73fac45ce8f5f4a514ee1f15e
Source dataset
uspto-grants-2014_09
Patent number
US08828996B2

Reaction notes

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