Ethyl Acetate → HCID 131729937, compound

HRID 1889137Notes

Reaction equation

HRID 1889137 reaction equation
[CH3:1][NH:2][CH2:3][CH2:4][C@@H:5]([C:7]1[S:8][CH:9]=[CH:10][CH:11]=1)[OH:6].C(OCC)(=O)C.[C:18]12([CH2:28][S:29](O)(=[O:31])=[O:30])[C:25]([CH3:27])([CH3:26])[CH:22]([CH2:23][CH2:24]1)[CH2:21][C:19]2=[O:20]>C(O)C>[CH3:26][C:25]1([CH3:27])[CH:22]2[CH2:23][CH2:24][C@@:18]1([CH2:28][S:29]([O:6][C@H:5]([C:7]1[S:8][CH:9]=[CH:10][CH:11]=1)[CH2:4][CH2:3][NH:2][CH3:1])(=[O:31])=[O:30])[C:19](=[O:20])[CH2:21]2

Participants

5

Reactant 3

HCID 8857Ethyl Acetate2×HCID 18462Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)-HCID 100950473-(N-Methylamino)-1-(2-thienyl)-1-propanol, (-)-

Product 1

HCID 131729937HCID 131729937, compoundYield 92.7%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
30 °C

Procedure

A mixture of (S)-3-methylamino-1-thiophen-2-yl-propan-1-ol (34.2 g, 200 mmol) and ethyl acetate (400 mL) is heated to 30° C., then a mixture of (+)-camphor-10-sulfonic acid (46.4 g, 200 mmol), ethyl acetate (100 mL) and ethanol (100 mL) is added dropwise at 30° C. in 40 minutes. At the end of the addition, the resulting solution is heated to 50° C., stirred for 15 minutes at that temperature, then cooled to 25° C. Once cold, the reaction mixture is concentrated to dryness and ethyl acetate (500 mL) is added to the residue. The resulting mixture is then heated to reflux, kept at that temperature for 15 minutes, then cooled to 25° C. in 30 minutes while seeding the reaction mixture when the temperature reaches about 40° C. Once cold, the resulting suspension is stirred for 30 additional minutes. Afterwards, the precipitate is filtrated, washed with ethyl acetate (2×50 mL) and dried at 40° C. under vacuum (20 mbar) for 15 h affording a white solid (71.5 g, 89%); 1H-NMR (CDCl3, 400 MHz): 7.2 (1 H, dm), 7.0 (1 H, m), 6.9 (1 H, m), 5.21 (1 H, t), 3.3 (3 H, m), 2.82 (1 H, d), 2.75 (3 H, s), 2.50 (1 H, m, symm.), 2.3 (3 H, m), 2.1 (1 H, m), 2.0 (1 H, m), 1.85 (1 H, d), 1.74 (1 H, m, symm.), 1.4 (1 H, m), 1.04 (3 H, s), 0.82 (3 H, s).

Workup

  1. additionis added dropwise at 30° C. in 40 minutes
  2. additionAt the end of the addition
  3. temperaturethe resulting solution is heated to 50° C.
  4. temperaturecooled to 25° C
  5. concentrationOnce cold, the reaction mixture is concentrated to dryness and ethyl acetate (500 mL)
  6. additionis added to the residue
  7. temperatureThe resulting mixture is then heated
  8. temperatureto reflux
  9. waitkept at that temperature for 15 minutes
  10. temperaturecooled to 25° C. in 30 minutes
  11. customreaches about 40° C
  12. stirringOnce cold, the resulting suspension is stirred for 30 additional minutes
  13. filtrationAfterwards, the precipitate is filtrated
  14. washwashed with ethyl acetate (2×50 mL)
  15. customdried at 40° C. under vacuum (20 mbar) for 15 h

Sources & evidence

ORD record
ord-3c4547611dec43b480308da466ffa3f7
Source dataset
uspto-grants-2013_08
Patent number
US08501967B2

Reaction notes

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