Toluene → 2-(6-Methoxy-2-naphthyl)propionic acid

HRID 363812Notes

Reaction equation

HRID 363812 reaction equation
C1(C)C=CC=CC=1.[CH3:8][O:9][C:10]1[CH:11]=[C:12]2[C:17](=[CH:18][CH:19]=1)[CH:16]=[C:15]([C@H:20]([CH3:24])[C:21]([OH:23])=[O:22])[CH:14]=[CH:13]2.[CH3:25][O:26][C:27]1[CH:28]=[C:29]2[C:34](=[CH:35][CH:36]=1)[CH:33]=[C:32]([CH:37]([CH3:41])[C:38]([OH:40])=[O:39])[CH:31]=[CH:30]2.[OH-].[Na+:43]>O>[CH3:8][O:9][C:10]1[CH:11]=[C:12]2[C:17](=[CH:18][CH:19]=1)[CH:16]=[C:15]([CH:20]([CH3:24])[C:21]([OH:23])=[O:22])[CH:14]=[CH:13]2.[CH3:25][O:26][C:27]1[CH:28]=[C:29]2[C:34](=[CH:35][CH:36]=1)[CH:33]=[C:32]([C@H:37]([CH3:41])[C:38]([O-:40])=[O:39])[CH:31]=[CH:30]2.[Na+:43]

Participants

7

Reactant 4

HCID 1140TolueneHCID 13022-(6-Methoxy-2-naphthyl)propionic acidHCID 14798Sodium HydroxideHCID 156391Naproxen

Product 2

HCID 13022-(6-Methoxy-2-naphthyl)propionic acidYield 91.64%HCID 23681059Naproxen Sodium

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Conditions

Temperature
85 °C

Procedure

Using the apparatus of the above Comparative Example, a toluene solution of 2-(6-methoxy-2-naphthyl)propionic acid (580.68 grams, 18.11 wt % solids, 91.64% S-enantiomer) was prepared from a sample of high chiral purity (S)-2-(6-methoxy-2-naphthyl)propionic acid, and racemic 2-(6-methoxy-2-naphthyl)propionic acid. The solution was heated to 85° C. Totals of 27.59 grams of 49.22 wt % NaOH and 7.822 grams of water were added. Two clear liquid phases were obtained. Water was stripped to 94.0° C. in 285 minutes. The total amount of water collected during the strip was 21.36 grams and the amount of toluene removed was 1.83 grams. The batch was agitated at 93.6°-94.0° C. for 15 minutes and cooled to 75° C. in 82 minutes and agitated at 75° C. for 60 minutes. Solids in the slurry settled well at the end of the 60-minute 75° C. ride. The centrifuge cake (sodium (S)-2-(6-methoxy-2-naphthyl)propionate monohydrate) was washed with 149.94 grams of hot (75° C.) toluene. Totals of 483.77 and 127.61 grams of mother liquor and wash liquor were recovered, respectively. The wet centrifuge cake weighed 75.02 grams which after drying for 8 hours at 80°-90° C. and under full vacuum yielded 67.29 grams of anhydrous sodium (S)-2-(6-methoxy-2-naphthyl)propionate. Chiral purities for the product and the mother liquor were found by analysis to be 99.03% S-enantiomer and 80.28% S-enantiomer, respectively.

Workup

  1. customTwo clear liquid phases were obtained
  2. customThe total amount of water collected during the strip
  3. customthe amount of toluene removed
  4. temperaturecooled to 75° C. in 82 minutes
  5. stirringagitated at 75° C. for 60 minutes
  6. customsettled well at the end of the 60-minute 75° C. ride
  7. washThe centrifuge cake (sodium (S)-2-(6-methoxy-2-naphthyl)propionate monohydrate) was washed with 149.94 grams of hot (75° C.) toluene
  8. washTotals of 483.77 and 127.61 grams of mother liquor and wash liquor
  9. customwere recovered
  10. customafter drying for 8 hours at 80°-90° C. and under full vacuum

Sources & evidence

ORD record
ord-b4d4f82fcc0f4beaa9dcc69005f1e4de
Source dataset
uspto-grants-1999_02
Patent number
US05874614

Reaction notes

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