Propionic Acid → 4-Chloro-6-methyl-10,10-dioxo-2-propionylamino-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carboxylic acid methyl ester

HRID 1173348Notes

Reaction equation

HRID 1173348 reaction equation
C(Cl)(=O)C(Cl)=O.[C:7](O)(=[O:10])[CH2:8][CH3:9].[CH3:12][O:13][C:14]([C:16]1[CH:17]=[C:18]([CH3:35])[C:19]2[O:25][C:24]3[C:26]([Cl:31])=[CH:27][C:28]([NH2:30])=[CH:29][C:23]=3[CH2:22][S:21](=[O:33])(=[O:32])[C:20]=2[CH:34]=1)=[O:15]>ClCCl.CN(C=O)C>[CH3:12][O:13][C:14]([C:16]1[CH:17]=[C:18]([CH3:35])[C:19]2[O:25][C:24]3[C:26]([Cl:31])=[CH:27][C:28]([NH:30][C:7](=[O:10])[CH2:8][CH3:9])=[CH:29][C:23]=3[CH2:22][S:21](=[O:33])(=[O:32])[C:20]=2[CH:34]=1)=[O:15]

Participants

6

Reactant 3

HCID 1032Propionic AcidHCID 65578Oxalyl chlorideHCID 115596902-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 117045214-Chloro-6-methyl-10,10-dioxo-2-propionylamino-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carboxylic acid methyl ester

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of oxalyl chloride (0.17 mL, 2.03 mmol) and propionic acid (0.15 mL, 2.03 mmol) in dichloromethane (20 mL) was stirred for 1 h. Compound of Example 1 (0.5 g, 1.35 mmol) in DMF (5 mL) was added to the reaction mixture at 25° C. and stirred for 18 h. The solvent was removed under vacuum, water (25 mL) was added and the solid precipitated was filtered. The crude product was purified by column chromatography (silica gel, 1% methanol in chloroform) to obtain the title compound. Yield: 0.28 g, (60%); mp: 226-228° C.; 1H NMR (DMSO-d6, 300 MHz): δ 1.06 (t, 3H, CH3), 2.33 (q, 2H, CH2), 2.64 (s, 3H, CH3), 3.85 (s, 3H, OCH3), 5.30 (s, 2H, CH2), 7.66 (d, 1H, Ar), 7.88 (s, 1H, Ar), 8.10 (s, 1H, Ar), 8.15 (s, 1H, Ar), 10.26 (s, 1H, NH); MS: m/e (EI) 423 (M+); analysis: C19H18ClNO6S requires C, 53.66; H, 4.28; N, 3.30; Cl, 8.32; S, 7.56. found: C, 53.38; H, 4.27; N, 3.48; Cl, 8.64; S, 7.75%.

Workup

  1. customThe solvent was removed under vacuum, water (25 mL)
  2. additionwas added
  3. customthe solid precipitated
  4. filtrationwas filtered
  5. customThe crude product was purified by column chromatography (silica gel, 1% methanol in chloroform)

Sources & evidence

ORD record
ord-9dd12f67a62b49678877feffc346b9e9
Source dataset
uspto-grants-2010_11
Patent number
US07834052B2

Reaction notes

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