Succinic Acid → HCID 66707315, compound

HRID 911484Notes

Reaction equation

HRID 911484 reaction equation
C(OC([N:8]1[CH2:14][CH2:13][C:12]2[C:15]([S:20][C:21](=O)N(C)C)=[C:16]([Cl:19])[CH:17]=[CH:18][C:11]=2[CH2:10][CH2:9]1)=O)(C)(C)C.[OH-].[K+].Cl.[N:29]1[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=1CCl.[C:37]([OH:44])(=[O:43])[CH2:38][CH2:39][C:40]([OH:42])=[O:41]>CO.C(O)(C)C.C1(C)C=CC=CC=1>[C:37]([OH:44])(=[O:43])[CH2:38][CH2:39][C:40]([OH:42])=[O:41].[Cl:19][C:16]1[CH:17]=[CH:18][C:11]2[CH2:10][CH2:9][NH:8][CH2:14][CH2:13][C:12]=2[C:15]=1[S:20][CH2:21][C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][N:29]=1

Participants

8

Reactant 4

HCID 1110Succinic AcidHCID 14797Potassium HydroxideHCID 23392Picolyl chloride hydrochlorideHCID 576559793-tert-butoxycarbonyl-7-chloro-6-dimethylaminocarbonylthio-2,3,4,5-tetrahydro-1H-benzo[d]azepine

Product 1

HCID 66707315HCID 66707315, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 1140TolueneSolventHCID 3776IsopropanolSolvent

Conditions

Temperature
60 °C

Procedure

Dissolve 3-tert-butoxycarbonyl-7-chloro-6-dimethylcarbamoylthio-2,3,4,5-tetrahydro-1H-benzo[d]azepine (1 equiv.) in methanol (0.1-0.4 M) and add potassium hydroxide (8-20 equiv.). Stir at 60° C. for 4-24 h. Cool the reaction mixture in an ice bath, add picolyl chloride hydrochloride (1-3 equiv.) and stir the mixture at ambient temperature for 16-24 h. Add a volume of toluene approximately equal to the volume of the reaction mixture and concentrate the resulting mixture to approximately ½ the resulting total volume and repeat this process once more. Add water until all solids dissolve and separate the layers. Dry the organic layer over Na2SO4 and filter. Heat the solution (containing about 0.25-0.40 M of free base of the title compound) to 50-75° C. and then optionally seed with previously formed crystals of the title compound. Add succinic acid (1-1.3 equivalents) in isopropyl alcohol (0.25-0.40M solution) to the solution over 545 min. Cool the solution to 20-25° C. over 1-3 h and filter, rinsing with a solution of toluene/isopropyl alcohol (1:1). Dry the resulting solid under vacuum at 50-70° C./5 Torr to give the title compound as a white solid, mp 159-160° C. Anal. Calc'd for C20H23ClN2O4S: C, 56.80; H, 5.48; N, 6.62. Found: C, 56.56; H, 5.41; N, 6.57.

Workup

  1. temperatureCool the reaction mixture in an ice bath
  2. stirringstir the mixture at ambient temperature for 16-24 h
  3. concentrationconcentrate the resulting mixture
  4. dissolutionAdd water until all solids dissolve
  5. customseparate the layers
  6. dry with materialDry the organic layer over Na2SO4
  7. filtrationfilter
  8. temperatureHeat the solution (
  9. additioncontaining about 0.25-0.40 M of free base of the title compound) to 50-75° C.
  10. temperatureCool the solution to 20-25° C. over 1-3 h
  11. filtrationfilter
  12. washrinsing with a solution of toluene/isopropyl alcohol (1:1)
  13. customDry the resulting solid under vacuum at 50-70° C./5 Torr

Sources & evidence

ORD record
ord-9932e82bd62e4b72967b18436c722ef8
Source dataset
uspto-grants-2011_09
Patent number
US08022062B2

Reaction notes

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