Sodium triacetoxyborohydride → Trecetilide

HRID 1767272Notes

Reaction equation

HRID 1767272 reaction equation
O[CH:2]1[O:6][C@H:5]([C:7]2[CH:12]=[CH:11][C:10]([NH:13][S:14]([CH3:17])(=[O:16])=[O:15])=[CH:9][CH:8]=2)[CH2:4][CH2:3]1.[CH2:18]([NH:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][C:26]([CH3:29])([F:28])[CH3:27])[CH3:19].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>CCOC(C)=O>[CH2:18]([N:20]([CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][C:26]([F:28])([CH3:29])[CH3:27])[CH2:2][CH2:3][CH2:4][C@@H:5]([C:7]1[CH:12]=[CH:11][C:10]([NH:13][S:14]([CH3:17])(=[O:16])=[O:15])=[CH:9][CH:8]=1)[OH:6])[CH3:19]

Participants

5

Reactant 3

HCID 5049666Sodium triacetoxyborohydrideHCID 9877517N-ethyl-6-methyl-6-fluoroheptane amineHCID 11357336N-[4-[(2S)-Tetrahydro-5-hydroxy-2-furanyl]phenyl]methanesulfonamide

Product 1

HCID 163300TrecetilideYield 92%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

N-[4-[(2S)-Tetrahydro-5-hydroxy-2-furanyl]phenyl]methanesulfonamide (10.0 g, 38.9 mmol) from Preparation 4 and N-ethyl-6-methyl-6-fluoroheptane amine (99% pure, 6.8 g, 38.9 mmol) from Preparation 7 were stirred with EtOAC (25 ml) in a flask for 1 hour. The slurry became clear solution, indicating formation of the iminium salt. Sodium triacetoxyborohydride (11.5 g, 54.4 mmol) was placed in a separate flask with EtOAc (50 ml). The mixture was cooled to 0° C. The first solution (iminium salt) was added slowly to the second mixture with vigorous stirring. The temperature was maintained at 0 to 4° C. After the addition was complete, the flask was rinsed with EtOAc (10 ml), and that was added also. The mixture was stirred overnight at 0° C. Water (100 ml) was added to quench the excess reagent, while the temperature was maintained at 0 to 4° C. While cooling was maintained, the pH was raised to 6.5 using a 10% aqueous sodium hydroxide solution. The layers were separated, and the aqueous was extracted with EtOAc (2×50 ml). The aqueous layer was then adjusted to pH 8.2, and the product was extracted with EtOAc (3×100 ml). The solvent was removed under reduced pressure to provide the title product as a colorless oil (14.9 g) in 92% yield. TLC 100% EtOAc, Rf=0.15.

Workup

  1. customfrom Preparation 7
  2. temperatureThe temperature was maintained at 0 to 4° C
  3. additionAfter the addition
  4. washthe flask was rinsed with EtOAc (10 ml)
  5. additionthat was added also
  6. stirringThe mixture was stirred overnight at 0° C
  7. additionWater (100 ml) was added
  8. customto quench the excess reagent
  9. temperaturewhile the temperature was maintained at 0 to 4° C
  10. temperatureWhile cooling
  11. temperaturewas maintained
  12. temperaturethe pH was raised to 6.5 using a 10% aqueous sodium hydroxide solution
  13. customThe layers were separated
  14. extractionthe aqueous was extracted with EtOAc (2×50 ml)
  15. extractionthe product was extracted with EtOAc (3×100 ml)
  16. customThe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-392de1dd85ed4ee18cc135e849ca1f7f
Source dataset
uspto-grants-2007_06
Patent number
US07232930B2

Reaction notes

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