Phenyl chloroformate → HCID 22620174, compound

HRID 840674Notes

Reaction equation

HRID 840674 reaction equation
Cl.[Cl:2][C:3]1[CH:8]=[CH:7][N:6]=[CH:5][CH:4]=1.[CH2:9]([Mg]Br)[CH2:10][CH2:11][CH2:12][CH3:13].Cl[C:17]([O:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)=[O:18]>C1COCC1>[Cl:2][C:3]1[CH:8]=[CH:7][N:6]([C:17]([O:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[O:18])[CH:5]([CH:9]2[CH2:13][CH2:12][CH2:11][CH2:10]2)[CH:4]=1

Participants

5

Reactant 3

HCID 15891Phenyl chloroformateHCID 818524-Chloropyridine hydrochlorideHCID 178445865HCID 178445865, compound

Product 1

HCID 22620174HCID 22620174, compoundYield 86.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a stirred mixture of 4-chloropyridine hydrochloride (3 g, 20 mmol) in 200 mL of THF at −78° C. was added 24 mL (48 mmol) of pentylmagnesium bromide (2M soln in ether) slowly dropwise. After being stirred at −78° C. for 20 minutes, phenyl chloroformate (2.51 mL, 20 mmol) was added and the mixture was stirred for 30 minutes at −78° C. The cooling bath was removed and the reaction mixture was allowed to stir while slowly warming to room temperature. Aqueous 20% NH4Cl (50 mL) and ether (80 mL) were added, the layers were separated, and the queous phase was extracted twice with ether. The combined organic extracts were washed successively with 50 mL portions of saturated aqueous CuSO4, water, saturated NaHCO3, and brine. The organic phase was dried over MgSO4, filtered through Celite, and evaporated to give the crude product. Purification by column chromatography (silica gel, 5% EtOAc in hexanes) afforded 5.25 g (86.4%) of the product as a yellow oil that was homogeneous by TLC analysis. 1H NMR (250 MHz) δ7.61-5.67 (m, 5 H), 5.66 (d, 1 H), 5.28 (m, 1 H), 5.01 (m, 1 H), 2.21 (m, 1 H), 1.98-1.28 (m, 8 H).

Workup

  1. stirringthe mixture was stirred for 30 minutes at −78° C
  2. customThe cooling bath was removed
  3. stirringto stir
  4. temperaturewhile slowly warming to room temperature
  5. additionAqueous 20% NH4Cl (50 mL) and ether (80 mL) were added
  6. customthe layers were separated
  7. extractionthe queous phase was extracted twice with ether
  8. washThe combined organic extracts were washed successively with 50 mL portions of saturated aqueous CuSO4, water, saturated NaHCO3, and brine
  9. dry with materialThe organic phase was dried over MgSO4
  10. filtrationfiltered through Celite
  11. customevaporated
  12. customto give the crude product
  13. customPurification by column chromatography (silica gel, 5% EtOAc in hexanes)

Sources & evidence

ORD record
ord-5b77181779a24d338882f6b475757ef4
Source dataset
uspto-grants-2002_04
Patent number
US06369078B1

Reaction notes

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