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 1695266Notes

Reaction equation

HRID 1695266 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 (El) 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-5d9ab1b9cab94fd387a28c0ac75ddf00
Source dataset
uspto-grants-2012_04
Patent number
US08163730B2

Reaction notes

Loading…