Hydrochloric Acid → 4-Chloro-2-[4-(2-hydroxy-ethyl)-piperazine-1-yl]-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carboxylic acid methyl ester

HRID 1172550Notes

Reaction equation

HRID 1172550 reaction equation
[CH2:1]([CH2:3][NH2:4])[OH:2].Cl[CH2:6][CH2:7][N:8]([CH2:31][CH2:32]Cl)[C:9]1[CH:29]=[C:28]([Cl:30])[C:12]2[O:13][C:14]3[C:23]([CH3:24])=[CH:22][C:21]([C:25]([OH:27])=[O:26])=[CH:20][C:15]=3[S:16](=[O:19])(=[O:18])[CH2:17][C:11]=2[CH:10]=1.O.Cl.[CH3:36]O>>[CH3:36][O:27][C:25]([C:21]1[CH:22]=[C:23]([CH3:24])[C:14]2[O:13][C:12]3[C:28]([Cl:30])=[CH:29][C:9]([N:8]4[CH2:7][CH2:6][N:4]([CH2:3][CH2:1][OH:2])[CH2:32][CH2:31]4)=[CH:10][C:11]=3[CH2:17][S:16](=[O:19])(=[O:18])[C:15]=2[CH:20]=1)=[O:26]

Participants

6

Reactant 5

HCID 313Hydrochloric AcidHCID 700EthanolamineHCID 887MethanolHCID 962WaterHCID 1317284742-[Bis-(2-chloroethyl)amino]-4-chloro-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]-cycloheptene-8-carboxylic acid

Product 1

HCID 116915114-Chloro-2-[4-(2-hydroxy-ethyl)-piperazine-1-yl]-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carboxylic acid methyl ester

Conditions

Temperature
70 °C

Procedure

Ethanol amine (0.25 mL, 4.17 mmol) was added to a solution of Example 102j (0.5 g, 1.04 mmol) in methanol (5 mL) in an atmosphere of nitrogen and sealed in a pressure reactor vessel at 120° C. for 4 h. It was brought to room temperature, treated with, chilled water, dilute HCl to neutral pH and extracted with n-butanol. The organic layer was washed with water, brine, dried, concentrated, treated with methanolic HCl solution, and refluxed at 70° C. for 3 h. The reaction mixture was concentrated, treated with aqueous sodium bicarbonate solution to neutral pH and extracted with ethyl acetate. The organic layer was washed with water, brine, dried, concentrated and purified using flash chromatography (silica gel, 5% methanol/chloroform) to obtain the title compound. Yield: 0.337 g, (67.13%); 1H NMR (DMSO-d6): δ 2.70 (s, 3H, CH3), 3.05-3.15 (m, 4H, 2CH2), 3.40-3.45 (m, 8H, 4CH2), 3.70 (s, 1H, OH), 3.90 (s, 3H, OCH3), 5.20 (s, 2H, CH2), 7.10 (s, 1H, Ar), 7.20 (s, 1H, Ar), 8.15 (s, 1H, Ar), 8.20 (s, 1H, Ar); MS: m/e (EI+) 481 (M+1).

Workup

  1. customsealed in a pressure reactor vessel at 120° C. for 4 h
  2. customwas brought to room temperature
  3. additiontreated with,
  4. extractionextracted with n-butanol
  5. washThe organic layer was washed with water, brine
  6. customdried
  7. concentrationconcentrated
  8. additiontreated with methanolic HCl solution
  9. concentrationThe reaction mixture was concentrated
  10. additiontreated with aqueous sodium bicarbonate solution to neutral pH
  11. extractionextracted with ethyl acetate
  12. washThe organic layer was washed with water, brine
  13. customdried
  14. concentrationconcentrated
  15. custompurified

Sources & evidence

ORD record
ord-e0b4f4e1ce224fafa1d115f20524d8db
Source dataset
uspto-grants-2010_11
Patent number
US07834001B2

Reaction notes

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