Sodium → 1,1-Dioxo-3-butyl-3-ethyl-5-phenyl-7-isopropoxy-8-carboxymethoxy-2,3,4,5-tetrahydro-1,5-benzothiazepine

HRID 458918Notes

Reaction equation

HRID 458918 reaction equation
[Na].[O:2]=[S:3]1(=[O:32])[C:9]2[CH:10]=[C:11]([O:15][CH2:16][C:17]([OH:19])=[O:18])[C:12](Br)=[CH:13][C:8]=2[N:7]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH2:6][C:5]([CH2:28][CH2:29][CH2:30][CH3:31])([CH2:26][CH3:27])[CH2:4]1>C(O)(C)C>[O:2]=[S:3]1(=[O:32])[C:9]2[CH:10]=[C:11]([O:15][CH2:16][C:17]([OH:19])=[O:18])[C:12]([O:15][CH:11]([CH3:12])[CH3:10])=[CH:13][C:8]=2[N:7]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH2:6][C:5]([CH2:28][CH2:29][CH2:30][CH3:31])([CH2:26][CH3:27])[CH2:4]1

Participants

4

Reactant 2

HCID 5360545Sodium2×HCID 223931311,1-Dioxo-3-butyl-3-ethyl-5-phenyl-7-bromo-8-carboxymethoxy-2,3,4,5-tetrahydro-1,5-benzothiazepine

Product 1

HCID 184424731,1-Dioxo-3-butyl-3-ethyl-5-phenyl-7-isopropoxy-8-carboxymethoxy-2,3,4,5-tetrahydro-1,5-benzothiazepineYield 81.7%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
80 °C

Procedure

To isopropyl alcohol (12 ml) was added sodium (115 mg, 5 mmol) and the temperature was then raised to 80° C. to let the alcohol salt form. After all the sodium was dissolved 1,1-dioxo-3-butyl-3-ethyl-5-phenyl-7-bromo-8-carboxymethoxy-2,3,4,5-tetrahydro-1,5-benzothiazepine (Method 9; 100 mg, 0.2 mmol) was added in one portion. The reaction was then refluxed overnight, and then cooled to room temperature and quenched with acetic acid. The solvent was then removed under reduced pressure and the residue was dissolved in water and MeCN (70/30) and partially purified by HPLC. The residue was dissolved in ethylene glycol and NaOH (500 mg) was added. This reaction mixture was heated to 125° C. overnight and then cooled to room temperature and quenched with acetic acid, and EtOAc (100 ml) was added. The ethylene glycol was removed by washing the organic layer with acidic water three times. The organic layer was then concentrated and the residue was purified again as above to give the title compound 40 mg (41%). NMR (300 MHz) 0.7–1.0 (m, 6H), 1.0–1.8 (m, 15H), 3.2 (q, 2H), 3.75 (m, 2H), 4.3 (m, 1H), 4.6 (s, 2H), 6.35 (s, 1H), 6.95–7.2 (m, 3H), 7.2–7.4 (m, 2H), 7.55 (s, 1H).

Workup

  1. additionwas added in one portion
  2. temperatureThe reaction was then refluxed overnight
  3. temperaturecooled to room temperature
  4. customquenched with acetic acid
  5. customThe solvent was then removed under reduced pressure
  6. dissolutionthe residue was dissolved in water
  7. customMeCN (70/30) and partially purified by HPLC
  8. dissolutionThe residue was dissolved in ethylene glycol
  9. additionNaOH (500 mg) was added
  10. temperatureThis reaction mixture was heated to 125° C. overnight
  11. temperaturecooled to room temperature
  12. customquenched with acetic acid, and EtOAc (100 ml)
  13. additionwas added
  14. customThe ethylene glycol was removed
  15. washby washing the organic layer with acidic water three times
  16. concentrationThe organic layer was then concentrated
  17. customthe residue was purified again as above

Sources & evidence

ORD record
ord-0a4016f7e3f540a3abba967f27b967fc
Source dataset
uspto-grants-2007_03
Patent number
US07192945B2

Reaction notes

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