Acetic Acid → 2-[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

HRID 1172536Notes

Reaction equation

HRID 1172536 reaction equation
[CH2:1]1[O:3][CH2:2]1.[NH2:4][C:5]1[CH:25]=[C:24]([Cl:26])[C:8]2[O:9][C:10]3[C:19]([CH3:20])=[CH:18][C:17]([C:21]([OH:23])=[O:22])=[CH:16][C:11]=3[S:12](=[O:15])(=[O:14])[CH2:13][C:7]=2[CH:6]=1.[C:27]([OH:30])(=O)[CH3:28].[C:31]([O-])([O-])=O.[Na+].[Na+]>O.C1COCC1>[CH3:31][O:22][C:21]([C:17]1[CH:18]=[C:19]([CH3:20])[C:10]2[O:9][C:8]3[C:24]([Cl:26])=[CH:25][C:5]([N:4]([CH2:2][CH2:1][OH:3])[CH2:28][CH2:27][OH:30])=[CH:6][C:7]=3[CH2:13][S:12](=[O:14])(=[O:15])[C:11]=2[CH:16]=1)=[O:23]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 6354Ethylene OxideHCID 10340Sodium CarbonateHCID 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 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

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
2.5 °C

Procedure

Ethylene oxide (40 mL) was added to a mixture of the ester of Example 35j (1 g, 2.72 mmol), acetic acid (15 mL) and water (15 mL) at 0-5° C. THF (2 mL) was added and the reaction mixture was stirred at 0-5° C. for 4 h and then left for overnight at room temperature. It was treated with water and aqueous Na2CO3 solution to neutral pH followed by extraction with ethyl acetate. The organic layer was washed with water, brine, dried, concentrated and purified using flash chromatography (silica gel) to obtain the title compound. Yield: 0.9 g, (73%); 1H NMR (DMSO-d6): δ 2.8 (s, 3H, CH3), 3.6 (t, 4H, 2CH2), 3.7, (t, 4H, 2CH2), 3.9, (s, 3H, OCH3), 5.2, (s, 2H, CH2) 6.9, (s, 2H, Ar), 8.2 (s, 2H, Ar); MS: m/e (CI+) 455 (M+1).

Workup

  1. waitleft for overnight at room temperature
  2. extractionfollowed by extraction with ethyl acetate
  3. washThe organic layer was washed with water, brine
  4. customdried
  5. concentrationconcentrated
  6. custompurified

Sources & evidence

ORD record
ord-5acc1e436a8046cf91a78091853bb545
Source dataset
uspto-grants-2010_11
Patent number
US07834001B2

Reaction notes

Loading…