Ethyl bromoacetate → 1,1-Dioxo-3-butyl-3-ethyl-5-phenyl-7-bromo-8-ethoxycarbonylmethoxy-2,3,4,5-tetrahydro-1,5-benzothiazepine

HRID 458516Notes

Reaction equation

HRID 458516 reaction equation
[O:1]=[S:2]1(=[O:27])[C:8]2[CH:9]=[C:10]([OH:14])[C:11]([Br:13])=[CH:12][C:7]=2[N:6]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH2:5][C:4]([CH2:23][CH2:24][CH2:25][CH3:26])([CH2:21][CH3:22])[CH2:3]1.Br[CH2:29][C:30]([O:32][CH2:33][CH3:34])=[O:31].C(=O)([O-])[O-].[Na+].[Na+]>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.CC#N>[O:27]=[S:2]1(=[O:1])[C:8]2[CH:9]=[C:10]([O:14][CH2:29][C:30]([O:32][CH2:33][CH3:34])=[O:31])[C:11]([Br:13])=[CH:12][C:7]=2[N:6]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH2:5][C:4]([CH2:23][CH2:24][CH2:25][CH3:26])([CH2:21][CH3:22])[CH2:3]1

Participants

6

Reactant 3

HCID 7748Ethyl bromoacetateHCID 10340Sodium CarbonateHCID 98250801,1-Dioxo-3-butyl-3-ethyl-5-phenyl-7-bromo-8-hydroxy-2,3,4,5-tetrahydro-1,5-benzothiazepine

Product 1

HCID 223931181,1-Dioxo-3-butyl-3-ethyl-5-phenyl-7-bromo-8-ethoxycarbonylmethoxy-2,3,4,5-tetrahydro-1,5-benzothiazepineYield 95.2%

Reagents, catalysts & solvents 2

HCID 74236Tetrabutylammonium BromideCatalystHCID 6342AcetonitrileSolvent

Procedure

A mixture of 1,1-dioxo-3-butyl-3-ethyl-5-phenyl-7-bromo-8-hydroxy-2,3,4,5-tetrahydro-1,5-benzothiazepine (WO 96/16051; 0.3 g), ethyl bromoacetate (0.14 g), sodium carbonate (0.3 g), tetrabutylammonium bromide (0.02 g) in MeCN (10 ml) were refluxed for 4 hours. The solvent was removed under reduced pressure. The residue was partitioned between DCM/H2O and the organic layer was separated. The solvent was evaporated and the residue was purified by chromatography (DCM/EtOAc, 90:10) to give the title compound 0.34 g (95%). NMR (500 Mz; CDCl3): 0.7–0.9 (m, 6H), 1.0–1.8 (m, 11H), 3.2 (m, 2H), 3.6–3.8 (br s, 2H), 4.3 (q, 2H), 4.7 (s, 2H), 7.0–7.1 (m, 3H), 7.15 (s, 1H), 7.3 (m, 2H), 7.4 (s, 1H).

Workup

  1. temperaturewere refluxed for 4 hours
  2. customThe solvent was removed under reduced pressure
  3. customThe residue was partitioned between DCM/H2O
  4. customthe organic layer was separated
  5. customThe solvent was evaporated
  6. customthe residue was purified by chromatography (DCM/EtOAc, 90:10)

Sources & evidence

ORD record
ord-192a554ffa0e44708defeb0acf3e5c75
Source dataset
uspto-grants-2007_03
Patent number
US07192946B2

Reaction notes

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