Ethyl Acetate → HCID 58420493, compound

HRID 1096522Notes

Reaction equation

HRID 1096522 reaction equation
[CH:1]1([N:4]2[C:13]3[C:8](=[CH:9][C:10]([F:19])=[C:11](F)[C:12]=3[O:14][CH:15]([F:17])[F:16])[C:7](=[O:20])[C:6]([C:21]([O:23][CH2:24][CH3:25])=[O:22])=[C:5]2[S:26]([CH3:29])(=[O:28])=[O:27])[CH2:3][CH2:2]1.CC[N:32]([CH:36]([CH3:38])C)[CH:33]([CH3:35])C.C[N:40](C)[C:41](=O)[CH3:42].[CH3:45]COC(C)=O>>[CH2:24]([O:23][C:21]([C:6]1[C:7](=[O:20])[C:8]2[C:13](=[C:12]([O:14][CH:15]([F:16])[F:17])[C:11]([N:32]3[CH2:33][CH2:35][C@@H:38]([C:41]([NH2:40])([CH3:42])[CH3:45])[CH2:36]3)=[C:10]([F:19])[CH:9]=2)[N:4]([CH:1]2[CH2:2][CH2:3]2)[C:5]=1[S:26]([CH3:29])(=[O:28])=[O:27])=[O:22])[CH3:25]

Participants

5

Reactant 4

HCID 8857Ethyl AcetateHCID 31374DimethylacetamideHCID 81531DiisopropylethylamineHCID 59687293HCID 59687293, compound

Product 1

HCID 58420493HCID 58420493, compound

Conditions

Temperature
80 °C

Procedure

A mixture containing compound (12) (3.0 g, 6.86 mmol), compound (10) (1.32 g, 10.3 mmol), anhydrous DIEA (6.03 ml, 34.3 mmol, dried over 4 Å sieves), and anhydrous N,N-dimethyl acetamide (DMA) (40 mL) is heated at 80° C. under an atmosphere of argon gas. After heating for 1 h, the reaction mixture is cooled to room temperature, diluted with EtOAc (200 mL), and washed with water (100 mL). The aqueous layer is extracted with EtOAc (100 mL), and the combined organic layers are washed with a saturated aqueous solution of sodium bicarbonate (100 mL). The organic layer is diluted with water (100 mL) and treated with an aqueous solution of HCl (4 N) until the aqueous layer is acidic (pH 2-3 after shaking the mixture vigorously). The organic layer is separated, and this process is repeated. The combined aqueous layers are diluted with EtOAc (100 mL) and treated with an aqueous solution of sodium hydroxide (6 N) until the aqueous layer is basic (pH ˜8 after shaking the mixture vigorously). The aqueous layer is separated, and this process is repeated. The combined organic layers are dried over magnesium sulfate, filtered, and concentrated under reduced pressure giving an orange solid (4.8 g). 1H-NMR (CDCl3): δ 0.36-0.41 (1H, m), 0.83-0.88 (1H, m), 0.98-1.03 (1H, m), 1.19 (6H, d, J=1.8 Hz), 1.18-1.26 (1H, m), 1.38 (3H, t, J=6.0 Hz), 1.71-1.78 (1H, m), 1.98-2.03 (1H, m), 2.22-2.34 (1H, m), 3.36-3.50 (2H, m), 3.43 (3H, s), 3.82-3.91 (1H, m), 4.02-4.13 (2H, m), 4.36-4.47 (2H, m), 6.19 (1H, t, J=75 Hz), 7.62 (1H, d, J=13.8 Hz); 19F: δ −121.3, −82.9 (d, J=39.5 Hz); LRMS calc. for C24H30F3N3O6S 545, found 546 (M+1).

Workup

  1. temperatureAfter heating for 1 h
  2. temperaturethe reaction mixture is cooled to room temperature
  3. washwashed with water (100 mL)
  4. extractionThe aqueous layer is extracted with EtOAc (100 mL)
  5. washthe combined organic layers are washed with a saturated aqueous solution of sodium bicarbonate (100 mL)
  6. additionThe organic layer is diluted with water (100 mL)
  7. additiontreated with an aqueous solution of HCl (4 N) until the aqueous layer
  8. customThe organic layer is separated
  9. additionThe combined aqueous layers are diluted with EtOAc (100 mL)
  10. additiontreated with an aqueous solution of sodium hydroxide (6 N) until the aqueous layer
  11. stirringafter shaking the mixture vigorously)
  12. customThe aqueous layer is separated
  13. dry with materialThe combined organic layers are dried over magnesium sulfate
  14. filtrationfiltered
  15. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-b9af47e0e57347dfac0df71f85fa74e7
Source dataset
uspto-grants-2012_03
Patent number
US08138346B2

Reaction notes

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