Acetic Acid → HCID 178514057, compound

HRID 1828394Notes

Reaction equation

HRID 1828394 reaction equation
[CH:1](O)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.N[C:16](N)=[S:17].Br.[NH2+:20]=[C:21](N)[OH:22].[OH-].[K+].ClCC(N)=[O:29].C(O)(=O)C.OO>O1CCCC1.O.O>[CH:5]1[CH:4]=[CH:3][C:2]([CH:1]([S+:17]([O-:29])[CH2:16][C:21]([NH2:20])=[O:22])[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)=[CH:7][CH:6]=1

Participants

11

Reactant 8

HCID 176Acetic AcidHCID 260Hydrogen BromideHCID 784Hydrogen PeroxideHCID 6580ChloroacetamideHCID 7037BenzhydrolHCID 14797Potassium HydroxideHCID 2723790ThioureaHCID 178512447HCID 178512447, compound

Product 1

HCID 178514057HCID 178514057, compoundYield 80.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 21881883Oxolane--water (1/1)Solvent2×

Conditions

Temperature
70 °C

Procedure

To a suspension of benzhydrol (35.00 g, 0.188 mol, 1 equivalent) and thiourea (17.40 g, 0.226 mol, 1.20 equivalents) in tetrahydrofuran/water (35.5 ml/52.5 ml), was added an aqueous 48% HBr solution (25.3 ml, 0.226 mol, 1.2 equivalents) over a 10 min period. During the addition, the reaction mixture is heated to 70° C. After 3 h stirring at 70° C., the uronium intermediate was hydrolyzed by addition of an aqueous 9.3N potassium hydroxide solution (58 ml, 0.542 mol, 2.88 equivalents) over a 55 min period. After 1.5 h stirring at 70° C., chloroacetamide (26.6 g, 0.282 mol, 1.5 equivalents) in a tetrahydrofuran/water (80 ml/79 ml) solution was added over 15 min. After 1 h stirring at 70° C., the reaction mixture was cooled down to 55° C. and the stirring was stopped. The lower aqueous phase was removed, and the reaction mixture was again stirred. Acetic acid (34.7 ml, 0.601 mol, 3.2 equivalents) was added. Hydrogen peroxide 30% (38.4 ml, 0.376 mol, 2 equivalents) was slowly added over 30 min. After 1 h stirring, the reaction mixture was cooled to 20° C. and water (263 ml) was added. The resultant suspension was stirred at 0° C. overnight. The suspension was then filtered and the solid was washed with water, and dried to yield modafinil (47.9 g, 80.4%). The crude modafinil was purified by recrystallization in methanol.

Workup

  1. additionDuring the addition
  2. stirringAfter 1.5 h stirring at 70° C.
  3. stirringAfter 1 h stirring at 70° C.
  4. temperaturethe reaction mixture was cooled down to 55° C.
  5. customThe lower aqueous phase was removed
  6. stirringthe reaction mixture was again stirred
  7. stirringAfter 1 h stirring
  8. temperaturethe reaction mixture was cooled to 20° C.
  9. filtrationThe suspension was then filtered
  10. washthe solid was washed with water
  11. customdried

Sources & evidence

ORD record
ord-53e3e77f76f942808ad2a4d62f2af6bf
Source dataset
uspto-grants-2006_06
Patent number
US07057069B2

Reaction notes

Loading…