Acetic Acid → HCID 14536609, compound

HRID 728725Notes

Reaction equation

HRID 728725 reaction equation
[ClH:1].[CH3:2][CH:3]([CH3:31])[CH2:4][CH2:5][NH:6][C:7]([C:9]1[CH:22]=[CH:21][C:20]2[S:19][C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[N:12]([CH:23]([CH3:30])[CH2:24][N:25]3[CH2:29][CH2:28][CH2:27][CH2:26]3)[C:11]=2[CH:10]=1)=S.Cl.C(O)(=[O:35])C>C(OCC)(=O)C.C(OCC)C>[ClH:1].[CH3:2][CH:3]([CH3:31])[CH2:4][CH2:5][NH:6][C:7]([C:9]1[CH:22]=[CH:21][C:20]2[S:19][C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[N:12]([CH:23]([CH3:30])[CH2:24][N:25]3[CH2:29][CH2:28][CH2:27][CH2:26]3)[C:11]=2[CH:10]=1)=[O:35]

Participants

6

Reactant 3

HCID 176Acetic AcidHCID 313Hydrochloric AcidHCID 14536603HCID 14536603, compound

Product 1

HCID 14536609HCID 14536609, compound

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

Mercuric acetate (0.668 g) is added with stirring to a suspension of N-(3-methylbutyl)-10-[(2RS)-1-(1-pyrolidinyl)-2-propyl]-2-phenothiazinecarbothioamide hydrochloride (1 g) in acetic acid (20 cc), and the mixture is left to react for 5 hours 30 minutes at a temperature in the region of 20° C. The reaction mixture is diluted with ethyl acetate (150 cc) and distilled water (50 cc) and then treated with caustic soda (d=1.33) to pH 13. The organic phase is separated and the aqueous phase is extracted again with ethyl acetate (2×50 cc). The combined organic phases are washed with saturated aqueous sodium hydrogen carbonate solution (100 cc) and then with saturated aqueous sodium chloride solution (100 cc), dried over magnesium sulphate, filtered and concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 40° C. The residual yellow oil (0.53 g) is purified by chromatography on a column (height: 30 cm; diameter: 2.5 cm) of silica gel (0.04-0.063 mm) under a slight excess pressure of nitrogen (40 kPa), eluting successively with a mixture (97.5:2.5 by volume) (100 cc) of methylene chloride and methanol and then with a mixture (95:5 by volume) (200 cc) of methylene chloride and methanol and collecting 15-cc fractions. Fractions 12 to 34 are combined and concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 40° C. The oil obtained is dissolved in ethyl acetate (10 cc) and a 3N solution (0.5 cc) of hydrochloric acid in ethyl ether is added. The solid formed is drained, washed with ethyl ether (2×2 cc) and dried under reduced pressure (5 mm Hg; 0.7 kPa) at 40° C. N-(3-Methylbutyl)-10-[(2RS)-1-(1-pyrrolidinyl)-2-propyl]-2-phenothiazinecarboxamide hydrochloride (0.37 g) is thereby obtained in the form of a pale yellow solid, m.p. about 100° C. (melts forming a paste), the NMR spectrum of which is identical to that of the product described below in Example 26.

Workup

  1. waitthe mixture is left
  2. customto react for 5 hours 30 minutes at a temperature in the region of 20° C
  3. distillationdistilled water (50 cc)
  4. additiontreated with caustic soda (d=1.33) to pH 13
  5. customThe organic phase is separated
  6. extractionthe aqueous phase is extracted again with ethyl acetate (2×50 cc)
  7. washThe combined organic phases are washed with saturated aqueous sodium hydrogen carbonate solution (100 cc)
  8. dry with materialwith saturated aqueous sodium chloride solution (100 cc), dried over magnesium sulphate
  9. filtrationfiltered
  10. concentrationconcentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 40° C
  11. customThe residual yellow oil (0.53 g) is purified by chromatography on a column (height: 30 cm; diameter: 2.5 cm) of silica gel (0.04-0.063 mm) under a slight excess pressure of nitrogen (40 kPa)
  12. washeluting successively with a mixture (97.5:2.5 by volume) (100 cc) of methylene chloride and methanol
  13. customwith a mixture (95:5 by volume) (200 cc) of methylene chloride and methanol and collecting 15-cc fractions
  14. concentrationconcentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 40° C
  15. customThe oil obtained
  16. customThe solid formed
  17. washwashed with ethyl ether (2×2 cc)
  18. customdried under reduced pressure (5 mm Hg; 0.7 kPa) at 40° C

Sources & evidence

ORD record
ord-81c00d0927964e82b64a6f33eb7d668b
Source dataset
uspto-grants-1991_09
Patent number
US05049669

Reaction notes

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