Sodium hydride → Carbonic acid, 3-cyclopropyl-3-oxetanyl 2-pyridinyl ester

HRID 1852162Notes

Reaction equation

HRID 1852162 reaction equation
[H-].[Na+].[CH:3]1([C:6]2([OH:10])[CH2:9][O:8][CH2:7]2)[CH2:5][CH2:4]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>C1COCC1.CCOC(C)=O.[Cl-].[Na+].O>[C:18](=[O:19])([O:17][C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][N:11]=1)[O:10][C:6]1([CH:3]2[CH2:5][CH2:4]2)[CH2:9][O:8][CH2:7]1

Participants

7

Reactant 3

HCID 24758Sodium hydrideHCID 2757370Carbonic acid di-2-pyridyl esterHCID 717427063-Cyclopropyloxetan-3-ol

Product 1

HCID 70979138Carbonic acid, 3-cyclopropyl-3-oxetanyl 2-pyridinyl esterYield 18.8%

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

To a suspension of sodium hydride, 60% in mineral oil (315 mg, 7.88 mmol) in THF (20 mL) was added 3-cyclopropyloxetan-3-ol (750 mg, 6.57 mmol) at 0° C. After stirring 30 min, the solution was transferred to a solution of di(pyridin-2-yl)carbonate (1421 mg, 6.57 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. The reaction was diluted with EtOAc followed by brine. The organic layer was collected, dried over MgSO4, filtered and evaporated to give the crude material. The crude material was purified via biotage (40 g column, 5-40% EtOAc:Hex) to give the expected product 3-cyclopropyloxetan-3-yl pyridin-2-yl carbonate (290 mg, 18.76% yield) as a clear thick oil. 1H NMR (400 MHz, CHLOROFORM-d) d 8.54-8.36 (m, 1H), 7.89-7.77 (m, 1H), 7.34-7.25 (m, 1H), 7.17 (d, J=8.3 Hz, 1H), 4.84 (d, J=8.5 Hz, 2H), 4.42 (d, J=8.3 Hz, 2H), 1.67-1.56 (m, 1H), 0.81-0.72 (m, 2H), 0.72-0.63 (m, 2H).

Workup

  1. stirringThe formed slurry was stirred at 0° C. for 30 min
  2. stirringstirred for 2 h
  3. customThe organic layer was collected
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. customevaporated
  7. customto give the crude material
  8. customThe crude material was purified via biotage (40 g column, 5-40% EtOAc:Hex)

Sources & evidence

ORD record
ord-206f36f88ed14c05a1f080ffb013d0db
Source dataset
uspto-grants-2015_02
Patent number
US08957203B2

Reaction notes

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