p-Toluenesulfonic acid → 4-Chloro-6-methyl-2-morpholin-4-yl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carboxylic acid methyl ester

HRID 2425104Notes

Reaction equation

HRID 2425104 reaction equation
C1(C)C=CC(S(O)(=O)=O)=CC=1.[CH3:12][O:13][C:14]([C:16]1[CH:17]=[C:18]([CH3:41])[C:19]2[O:25][C:24]3[C:26]([Cl:37])=[CH:27][C:28]([N:30]([CH2:34][CH2:35][OH:36])[CH2:31][CH2:32]O)=[CH:29][C:23]=3[CH2:22][S:21](=[O:39])(=[O:38])[C:20]=2[CH:40]=1)=[O:15].C(=O)(O)[O-].[Na+]>C1(C)C(C)=CC=CC=1.O>[CH3:12][O:13][C:14]([C:16]1[CH:17]=[C:18]([CH3:41])[C:19]2[O:25][C:24]3[C:26]([Cl:37])=[CH:27][C:28]([N:30]4[CH2:31][CH2:32][O:36][CH2:35][CH2:34]4)=[CH:29][C:23]=3[CH2:22][S:21](=[O:38])(=[O:39])[C:20]=2[CH:40]=1)=[O:15]

Participants

6

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 516892Sodium BicarbonateHCID 116410772-[Bis-(2-hydroxy-ethyl)-amino]-4-chloro-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda *6*-thia-dibenzo[a,d]cycloheptene-8-carboxylic acid methyl ester

Product 1

HCID 115249384-Chloro-6-methyl-2-morpholin-4-yl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carboxylic acid methyl ester

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 7237O-XyleneSolvent

Procedure

Catalytic amount of p-toluene sulphonic acid (PTSA) was added to a stirred solution of compound of Example 13 (1 g, 2.19 mmol) in xylene (50 mL). Reaction mixture was refluxed in Dean-Stark apparatus for 6 h and xylene was removed by distillation. Reaction mixture was diluted with 50 mL water, neutralized using 10% sodium bicarbonate solution and extracted using ethyl acetate (3×50 mL), washed with brine (2×10 mL), dried on sodium sulphate. The crude product obtained was purified by column chromatography (silica gel, ethylacetate/pet. ether) to obtain the title compound. Yield: 0.32 g, (33%); mp: >320° C.; 1H NMR (DMSO-d6, 300 MHz): δ 2.68 (s, 3H, CH3), 3.15 (s, 4H, 2CH2), 3.74 (s, 4H, 2CH2), 3.90 (s, 3H, OCH3), 4.65 (s, 2H, CH2), 6.76 (s, 1H, Ar), 6.88 (s, 1H, Ar), 8.06 (s, 1H, Ar), 8.44 (s, 1H, Ar); MS: m/e (EI) 437 (M+).

Workup

  1. customReaction mixture
  2. temperaturewas refluxed in Dean-Stark apparatus for 6 h
  3. customxylene was removed by distillation
  4. customReaction mixture
  5. extractionextracted
  6. washwashed with brine (2×10 mL)
  7. customdried on sodium sulphate
  8. customThe crude product obtained
  9. customwas purified by column chromatography (silica gel, ethylacetate/pet. ether)

Sources & evidence

ORD record
ord-9ce8b48a68d046bdb586fe1860d6c223
Source dataset
uspto-grants-2011_06
Patent number
US07964631B2

Reaction notes

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