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

HRID 458913Notes

Reaction equation

HRID 458913 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 MHz) 0.7–0.9 (m, 6H), 1.0–1.8 (m, 11H), 3.2 (m, 2H), 3.6–3.8 (brs, 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-90a33a27ceff47788a0013de59233911
Source dataset
uspto-grants-2007_03
Patent number
US07192945B2

Reaction notes

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