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 1695272Notes

Reaction equation

HRID 1695272 reaction equation
[CH2:1]1[O:3][CH2:2]1.[CH3:4][O:5][C:6]([C:8]1[CH:9]=[C:10]([CH3:27])[C:11]2[O:17][C:16]3[C:18]([Cl:23])=[CH:19][C:20]([NH2:22])=[CH:21][C:15]=3[CH2:14][S:13](=[O:25])(=[O:24])[C:12]=2[CH:26]=1)=[O:7].C(=O)(O)[O-].[Na+].[C:33](O)(=[O:35])[CH3:34]>O.C1COCC1>[CH3:4][O:5][C:6]([C:8]1[CH:9]=[C:10]([CH3:27])[C:11]2[O:17][C:16]3[C:18]([Cl:23])=[CH:19][C:20]([N:22]([CH2:2][CH2:1][OH:3])[CH2:34][CH2:33][OH:35])=[CH:21][C:15]=3[CH2:14][S:13](=[O:25])(=[O:24])[C:12]=2[CH:26]=1)=[O:7]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 6354Ethylene OxideHCID 516892Sodium BicarbonateHCID 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 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 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
25 °C

Procedure

Ethylene oxide (120 mL) was added to a stirred solution of compound of Example 1 (4.5 g, 12.26 mmol) in acetic acid (50 mL), water (50 mL) and THF (20 mL) mixture at −70° C., over a period of 1 h and then stirred at 25° C. for 14 h. The reaction mixture was cooled; pH was adjusted to 7 using 10% aqueous solution of sodium bicarbonate. The reaction mixture was extracted with ethyl acetate (3×250 mL). Combined organic layer was washed with brine (2×100 mL) and dried over sodium sulphate. Solvent was removed and the resulting crude product was purified by column chromatography (silica gel, ethyl acetate/pet ether) to obtain the title compound. Yield: 4 g (72%); mp 199-201° C.; 1H NMR (DMSO-d6, 300 MHz): δ 2.62 (s, 3H, CH3), 3.40 (t, 4H, 2CH2), 3.51 (t, 4H, 2CH2), 3.85 (s, 3H, OCH3), 4.80 (t, 2H, 2OH), 5.11 (s, 2H, CH2), 6.76 (s, 1H, Ar), 6.83 (s, 1H, Ar), 8.06 (s,1H, Ar), 8.13 (s,1H, Ar); MS: m/e (ES+) 456 (M+1).

Workup

  1. temperatureThe reaction mixture was cooled
  2. extractionThe reaction mixture was extracted with ethyl acetate (3×250 mL)
  3. washCombined organic layer was washed with brine (2×100 mL)
  4. dry with materialdried over sodium sulphate
  5. customSolvent was removed
  6. customthe resulting crude product was purified by column chromatography (silica gel, ethyl acetate/pet ether)

Sources & evidence

ORD record
ord-bd154279ddde472eaa5abb4b55bff317
Source dataset
uspto-grants-2012_04
Patent number
US08163730B2

Reaction notes

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