Sodium hydride → 4-methyltetrahydro-2H-pyran-4-yl pyridin-2-yl carbonate

HRID 1852165Notes

Reaction equation

HRID 1852165 reaction equation
[H-].[Na+].[CH3:3][C:4]1([OH:10])[CH2:9][CH2:8][O:7][CH2:6][CH2:5]1.[N:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[O:17][C:18](=O)[O:19]C1C=CC=CN=1.[NH4+].[Cl-]>C1COCC1.CCOCC>[C:18](=[O:19])([O:17][C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][N:11]=1)[O:10][C:4]1([CH3:3])[CH2:9][CH2:8][O:7][CH2:6][CH2:5]1

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 2757370Carbonic acid di-2-pyridyl esterHCID 123471184-Methyloxan-4-ol

Product 1

HCID 709786674-methyltetrahydro-2H-pyran-4-yl pyridin-2-yl carbonate

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a suspension of sodium hydride, 60% in mineral oil (207 mg, 5.17 mmol) in THF (20 mL) was added 4-methyltetrahydro-2H-pyran-4-ol (500 mg, 4.30 mmol) at 0° C. After stirring 30 min, the solution was transferred to a solution of di(pyridin-2-yl)carbonate (931 mg, 4.30 mmol) in THF (20 mL) through a cannula. The formed slurry was stirred at 0° C. for 30 min. The slurry was warmed to rt and stirred for 2 h. At room temperature, to the reaction mixture was added sat. aq. NH4Cl (1 mL) upon which brief and significant effervescence was observed. The mixture was transferred to a 250 mL separatory funnel and was diluted with Et2O (50 mL). The solution was washed with water:brine (25 mL: 25 mL). The aq. phase was extracted with EtOAc (100 mL). The combined organics were dried over MgSO4; filtered; then concentrated in vacuo. The resulting residue was dissolved in acetone and then concentrated onto Celite in vacuo. The resulting powder was subjected to SiO2 purification on the Biotage system [90 g SiO2 column, hexanes:EtOAc 90:10 to 60:40 over 8 CV] to get the product as a clear oil. 1H NMR (400 MHz, CHLOROFORM-d) δ 8.48-8.39 (m, 1H), 7.87-7.76 (m, 1H), 7.30-7.24 (m, 2H), 7.16-7.09 (m, 1H), 3.83-3.69 (m, 4H), 2.29-2.16 (m, 2H), 1.80 (ddd, J=14.3, 8.9, 5.9 Hz, 2H), 1.66 (s, 3H).

Workup

  1. stirringThe formed slurry was stirred at 0° C. for 30 min
  2. stirringstirred for 2 h
  3. customThe mixture was transferred to a 250 mL separatory funnel
  4. washThe solution was washed with water
  5. extractionThe aq. phase was extracted with EtOAc (100 mL)
  6. dry with materialThe combined organics were dried over MgSO4
  7. filtrationfiltered
  8. concentrationthen concentrated in vacuo
  9. dissolutionThe resulting residue was dissolved in acetone
  10. concentrationconcentrated onto Celite in vacuo
  11. customThe resulting powder was subjected to SiO2 purification on the Biotage system [90 g SiO2 column, hexanes:EtOAc 90:10 to 60:40 over 8 CV]

Sources & evidence

ORD record
ord-cadf936a65c94e8292ca49c2dd021f7c
Source dataset
uspto-grants-2015_02
Patent number
US08957203B2

Reaction notes

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