Hydrochloric Acid → HCID 19077626, compound

HRID 964614Notes

Reaction equation

HRID 964614 reaction equation
[CH3:1][C:2]1([C:9]2[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[CH:11][CH:10]=2)[NH:6][C:5](=O)N[C:3]1=[O:8].[OH-:17].[Na+].Cl.[C:20](OC(=O)C)(=O)C.[OH2:27]>>[C:5]([NH:6][C:2]([CH3:1])([C:9]1[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[CH:11][CH:10]=1)[C:3]([OH:8])=[O:27])(=[O:17])[CH3:20]

Participants

6

Reactant 5

HCID 313Hydrochloric AcidHCID 962Water2×HCID 7918Acetic AnhydrideHCID 14798Sodium Hydroxide2×HCID 2113515-(p-methoxyphenyl)-5-methyl-hydantoi

Product 1

HCID 19077626HCID 19077626, compoundYield 95%

Procedure

To a suspension of 5-methyl-5-(4-methoxyphenyl)hydantoin (90 g, 0.408 mol) in 360 mL of water was added solid NaOH (90 g, 2.246 mol) and the final solution was heated to reflux for 30 hours. After cooling to room temperature, 720 mL of water was added; the solution was cooled to 10° C. and the pH was adjusted to 9 with 2N HCl. Acetic anhydride (1.28 mol, 121 mL) was added dropwise as the pH was kept at 9 by simultaneous addition of 2N NaOH (1410 mL). After stirring the final solution for 1 hour at room temperature, a small amount of insoluble material was removed by filtration through a Celite® pad which was then washed with water. The pH of the filtrate was adjusted to 1 with 12N HCl. After stirring for 15 minutes at 10° C., the precipitated material was filtered, washed with water (3×250 mL), and dried in vacuo at 40° C. to yield racemic α-acetamido-4-methoxy-α-methylbenzeneacetic acid (92.34 g, 95%, mp: 222° C.). A suspension of racemic α-acetamido-4-methoxy-α-methylbenzeneacetic acid (90.3 g. 381 mmol) in 4515 mL of EtOH (50 v/w) was heated to 40° C. (internal). To this suspension was added 49.12 mL (381 mmol) of (L)-(-)-α-methylbenzylamine. The warm solution was seeded with a few crystals of (S)-(+)-α-acetamido-4-methoxy-α-methylbenzeneacetic acid and stirred at room temperature (24° C.) for 24 hours. The desired diastereomeric salt was collected by filtration, washed with EtOH (2×75 mL) and several times with Et2O and dried in vacuo at 40° C. to yield 38.95 g (57% optical yield). αD : +67.8° (MeOH, c=1).

Workup

  1. temperatureto reflux for 30 hours
  2. temperaturethe solution was cooled to 10° C.
  3. customa small amount of insoluble material was removed by filtration through a Celite® pad which
  4. washwas then washed with water
  5. filtrationthe precipitated material was filtered
  6. washwashed with water (3×250 mL)
  7. customdried in vacuo at 40° C.

Sources & evidence

ORD record
ord-0c34cc8f557e4ec291689110664eac23
Source dataset
uspto-grants-1998_06
Patent number
US05770615

Reaction notes

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