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

HRID 1927464Notes

Reaction equation

HRID 1927464 reaction equation
[BH4-].[Na+].[Cl:3][CH2:4][C:5](O)=O.[NH2:8][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.[C:31](=O)(O)[O-].[Na+]>C1C=CC=CC=1.O1CCCC1>[CH3:31][O:26][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]([NH:8][CH2:5][CH2:4][Cl:3])=[CH:10][C:11]=3[CH2:17][S:16](=[O:18])(=[O:19])[C:15]=2[CH:20]=1)=[O:27]

Participants

7

Reactant 4

HCID 300Chloroacetic AcidHCID 516892Sodium BicarbonateHCID 4311764Sodium borohydrideHCID 116317172-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 1317284464-Chloro-2-(2-chloro-ethylamino)-6-methyl-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 241BenzeneSolventHCID 8028TetrahydrofuranSolvent

Procedure

Sodiumborohydride (1.77 g, 46.78 mmol) was added portionwise to a stirred solution of chloro-acetic acid (7.71 g, 81.59 mmol) in benzene (270 mL) and dry tetrahydrofuran (30 mL) under nitrogen atmosphere at 15° C. The reaction mixture was stirred for 1 h, treated with the methyl ester of Example 35j (5 g, 13.61 mmol) and refluxed for 0.5 h. The reaction mixture was treated with 10% aqueous sodium bicarbonate solution and extracted with ethyl acetate. The organic layer was washed with water, brine, dried, concentrated and purified by crystallization (ethyl acetate/hexane) to obtain the title compound as a white solid. Yield: 5.25 g, (90%); mp: 224-225° C.; 1H NMR (DMSO-d6): δ 2.71 (s, 3H, CH3), 3.45 (t, 2H, CH2), 3.75 (t, 2H, CH2), 3.92 (s, 3H, OCH3), 5.15 (s, 2H, CH2), 6.53 (t, 1H, NH), 6.65-6.79 (m, 2H, Ar), 8.10 (s, 1H, Ar), 8.15 (s, 1H, Ar). MS: m/e (ES+) 431 (M+1).

Workup

  1. temperaturerefluxed for 0.5 h
  2. extractionextracted with ethyl acetate
  3. washThe organic layer was washed with water, brine
  4. customdried
  5. concentrationconcentrated
  6. custompurified by crystallization (ethyl acetate/hexane)

Sources & evidence

ORD record
ord-3b35277632114d56b94e3f55d87ac475
Source dataset
uspto-grants-2012_05
Patent number
US08183234B2

Reaction notes

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