Ethyl chloroformate → (2-{5-[2-(5-Fluoro-2-methoxy-phenyl)-ethyl]-tetrahydro-furan-2-yl}-ethyl)-carbamic ethyl ester

HRID 1919540Notes

Reaction equation

HRID 1919540 reaction equation
C([O-])([O-])=O.[K+].[K+].Cl[C:8]([O:10][CH2:11][CH3:12])=[O:9].[NH2:13][CH2:14][CH2:15][CH:16]1[CH2:20][CH2:19][CH:18]([CH2:21][CH2:22][C:23]2[CH:28]=[C:27]([F:29])[CH:26]=[CH:25][C:24]=2[O:30][CH3:31])[O:17]1.C([O-])(O)=O.[Na+]>C1COCC1.CO.C(Cl)Cl>[CH2:11]([O:10][C:8](=[O:9])[NH:13][CH2:14][CH2:15][CH:16]1[CH2:20][CH2:19][CH:18]([CH2:21][CH2:22][C:23]2[CH:28]=[C:27]([F:29])[CH:26]=[CH:25][C:24]=2[O:30][CH3:31])[O:17]1)[CH3:12]

Participants

7

Reactant 4

HCID 10928Ethyl chloroformateHCID 11430Potassium CarbonateHCID 516892Sodium BicarbonateHCID 11587069Tetrahydrofuranyl ethylamine, 14

Product 1

HCID 25258808(2-{5-[2-(5-Fluoro-2-methoxy-phenyl)-ethyl]-tetrahydro-furan-2-yl}-ethyl)-carbamic ethyl ester

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 21226129Dichloromethane methanolSolvent

Conditions

Temperature
0 °C

Procedure

Into a flame dried 20 mL vial was placed K2CO3 (239 mg, 1.73 mmol, 6.0 eq) and anhydrous THF (5.0 mL). The vial was purged with Ar(g) and then cooled in an ice bath. Ethyl chloroformate (156 mg, 1.44 mmol, 5.0 eq) was then added via syringe followed by slow addition of 14 (77 mg, 0.29 mmol, 1.0 eq) dissolved in THF (1.5 mL). The reaction was stirred at 0° C. for 0.5 hrs and then warmed to rt and allowed to stir an additional 3 hrs. The reaction was then stopped with sat. NaHCO3(aq) and extracted with EtOAc (3×20 mL). The organic layer was washed with brine and dried over Na2SO4, filtered, and concentrated under reduced pressure to yield crude product that was used in the next step of the synthesis. TLC: MeOH/CH2Cl2 (2:98, v:v), Rf 0.4; 1H NMR (CDCl3, 500 MHz) 6.87-6.82 (m, 2 H), 6.74-6.71 (m, 1 H), 4.12 (q, J=7.1 Hz, 2 H), 4.05-3.77 (m, 2 H), 3.78 (s, 3 H), 2.71-2.56 (m, 2 H), 2.08-1.51 (m, 10 H) 1.3 (t, J=7.2 Hz, 3 H). LRMS (ESI) [M+H]+ calcd for C18H27FNO4 340 found 340.

Workup

  1. customInto a flame dried 20 mL
  2. customThe vial was purged with Ar(g)
  3. temperaturecooled in an ice bath
  4. temperaturewarmed to rt
  5. stirringto stir an additional 3 hrs
  6. extractionextracted with EtOAc (3×20 mL)
  7. washThe organic layer was washed with brine
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customto yield crude product that
  12. customwas used in the next step of the synthesis

Sources & evidence

ORD record
ord-0b4d62816ea646699435e35a6f951594
Source dataset
uspto-grants-2012_05
Patent number
US08168635B2

Reaction notes

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