p-Toluenesulfonic acid → HCID 13823434, compound

HRID 1085327Notes

Reaction equation

HRID 1085327 reaction equation
C([O-])([O-])=O.[Na+].[Na+].Cl.C1([C@@H]2CCCC[C@H]2[O:20][C:21](=O)[C@H:22]([OH:44])[C@@H:23]([S:32][C:33]2[C:42]3[C:37](=[CH:38][CH:39]=[CH:40][CH:41]=3)[CH:36]=[CH:35][C:34]=2[NH2:43])[C:24]2[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[CH:26][CH:25]=2)C=CC=CC=1.C(Cl)Cl.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C(C)=CC=CC=1>[OH:44][C@@H:22]1[C@H:23]([C:24]2[CH:25]=[CH:26][C:27]([O:30][CH3:31])=[CH:28][CH:29]=2)[S:32][C:33]2[C:42]3[C:37]([CH:36]=[CH:35][C:34]=2[NH:43][C:21]1=[O:20])=[CH:38][CH:39]=[CH:40][CH:41]=3

Participants

6

Reactant 4

HCID 6101p-Toluenesulfonic acidHCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 86744730HCID 86744730, compound

Product 1

HCID 13823434HCID 13823434, compoundYield 89%

Reagents, catalysts & solvents 1

HCID 7237O-XyleneSolvent

Procedure

A 10-gallon extractor was charged with 12.0 L of 3N Na2CO3, 575 g (1.02 mole) of (2S,3S)-3-[(2-amino-1-naphthalenyl)thio]-2-hydroxy-3-(4-methoxyphenyl) propanoic acid (1R,2S)-2-phenylcyclohexyl ester hydrochloride and 8.0 L of methylene chloride. The aqueous layer was successively extracted with an additional 4L+2L=6.0 L of methylene chloride. The combined organic layers were dried by filtration through a pad of anhydrous potassium carbonate and evaporated in vacuo to afford the free base which was taken up in 11.5 L of xylene. Then 16 g of p-toluene sulfonic acid.monohydrate was added and this mixture was stirred at reflux under argon for 16 hours (overnight). After cooling, the product was collected by filtration, washed with 500 mL of ethyl acetate, followed by 3×500 mL =1.5 L of ether and air dried overnight to afford 318 g (89%) of (2 S,3S)-2,3-dihydro-3-hydroxy-2-(4-methoxyphenyl)-naphtho-[1,2-b][1,4]thiazepin-4(5H)-one as colorless needles, m.p. 235-238° decomposition, [α]D20 =+24.87°(c=0.4; acetone).

Workup

  1. extractionThe aqueous layer was successively extracted with an additional 4L+2L=6.0 L of methylene chloride
  2. dry with materialThe combined organic layers were dried by filtration through a pad of anhydrous potassium carbonate
  3. customevaporated in vacuo
  4. customto afford the free base which
  5. temperatureat reflux under argon for 16 hours (overnight)
  6. temperatureAfter cooling
  7. filtrationthe product was collected by filtration
  8. washwashed with 500 mL of ethyl acetate
  9. customdried overnight

Sources & evidence

ORD record
ord-afc99d12929d4504b146315bf4596a13
Source dataset
uspto-grants-1991_04
Patent number
US05008411

Reaction notes

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