Acetic Acid → HCID 44546893, compound

HRID 1967428Notes

Reaction equation

HRID 1967428 reaction equation
C[O:2][C:3]1[CH:12]=[C:11]2[C:6]([C@H:7]([C:14]3[CH:23]=[CH:22][C:21]4[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=4)[CH:15]=3)[CH2:8][N:9]([CH3:13])[CH2:10]2)=[CH:5][CH:4]=1.CC(O)=O>Br>[CH3:13][N:9]1[CH2:8][C@@H:7]([C:14]2[CH:23]=[CH:22][C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[CH:15]=2)[C:6]2[C:11](=[CH:12][C:3]([OH:2])=[CH:4][CH:5]=2)[CH2:10]1

Participants

4

Reactant 2

HCID 176Acetic AcidHCID 44546894HCID 44546894, compound

Product 1

HCID 44546893HCID 44546893, compound

Reagents, catalysts & solvents 1

HCID 260Hydrogen BromideSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of Compound 7 (42.5 g, 140 mmol) in 48% HBr (200 mL) was added AcOH (100 mL) to give a light yellow suspension. The reaction was heated to give a light yellow solution and stirred at 120° C. for 6 hr (<1.5% starting material left by HPLC), then concentrated. Dichloromethane (500 mL) was added to the residue and the suspension was filtered. The filtrate was neutralized with ice water, 50% NaOH (added slowly) and Na2CO3 solution to pH of 10. The aqueous layer was extracted with dichloromethane twice. The solid was fully dissolved in dichloromethane and triethylamine (25 mL), and washed with Na2CO3 solution to pH of 10. The organic layers were combined and washed with NaHCO3 and brine, dried over Na2SO4 overnight, filtered and concentrated. The crude product Compound 8, as the free base, can be used in the next step without further purification.

Workup

  1. customto give a light yellow suspension
  2. temperatureThe reaction was heated
  3. customto give a light yellow solution
  4. wait(<1.5% starting material left by HPLC)
  5. concentrationconcentrated
  6. additionDichloromethane (500 mL) was added to the residue
  7. filtrationthe suspension was filtered
  8. additionadded slowly) and Na2CO3 solution to pH of 10
  9. extractionThe aqueous layer was extracted with dichloromethane twice
  10. dissolutionThe solid was fully dissolved in dichloromethane
  11. washtriethylamine (25 mL), and washed with Na2CO3 solution to pH of 10
  12. washwashed with NaHCO3 and brine
  13. dry with materialdried over Na2SO4 overnight
  14. filtrationfiltered
  15. concentrationconcentrated
  16. customThe crude product Compound 8, as the free base, can be used in the next step without further purification

Sources & evidence

ORD record
ord-09aba0a988e54a569ee0a7cd517f53b6
Source dataset
uspto-grants-2013_04
Patent number
US08420811B2

Reaction notes

Loading…