Ethyl bromoacetate → HCID 22393110, compound

HRID 458519Notes

Reaction equation

HRID 458519 reaction equation
[O:1]=[S:2]1(=[O:29])[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]([CH2:25][CH2:26][CH2:27][CH3:28])([CH2:21][CH2:22][CH2:23][CH3:24])[CH2:3]1.Br[CH2:31][C:32]([O:34][CH2:35][CH3:36])=[O:33].C(=O)([O-])[O-].[Na+].[Na+]>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.CC#N>[O:29]=[S:2]1(=[O:1])[C:8]2[CH:9]=[C:10]([O:14][CH2:31][C:32]([O:34][CH2:35][CH3:36])=[O:33])[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]([CH2:25][CH2:26][CH2:27][CH3:28])([CH2:21][CH2:22][CH2:23][CH3:24])[CH2:3]1

Participants

6

Reactant 3

HCID 7748Ethyl bromoacetateHCID 10340Sodium CarbonateHCID 22393125HCID 22393125, compound

Product 1

HCID 22393110HCID 22393110, compoundYield 93%

Reagents, catalysts & solvents 2

HCID 74236Tetrabutylammonium BromideCatalystHCID 6342AcetonitrileSolvent

Procedure

1,1-Dioxo-3,3-dibutyl-5-phenyl-7-bromo-8-hydroxy-2,3,4,5-tetrahydro-1,5-benzothiazepine (synthesised by the procedure of WO9616051 for the corresponding 3-butyl-3-ethyl analogue; 2.0 g, 4.16 mmol), ethyl bromoacetate (0.84 g, 5.03 mmol), sodium carbonate (2.0 g, 18.9 mmol) and tetrabutylammonium bromide (80 mg, 0.25 mmol) were added to MeCN (20 ml). The mixture was refluxed for 2 hours and then evaporated under reduced pressure. The residue was extracted with DCM/water. The DCM layer was separated and evaporated under reduced pressure. The residue was purified by column chromatography on silica gel. The product was eluted with DCM /EtOAc (90:10) to give the title compound 2.2 g (93%). NMR (400 MHz) 0.7–0.8 (m, 6H), 1.0–1.6 (m, 15H), 3.2 (brs, 2H), 3.7 (brs, 2H), 4.3 (q, 2H), 4.7 (s, 2H), 7.0–7.3 (m, 6H), 7.4 (s, 1H).

Workup

  1. temperatureThe mixture was refluxed for 2 hours
  2. customevaporated under reduced pressure
  3. extractionThe residue was extracted with DCM/water
  4. customThe DCM layer was separated
  5. customevaporated under reduced pressure
  6. customThe residue was purified by column chromatography on silica gel
  7. washThe product was eluted with DCM /EtOAc (90:10)

Sources & evidence

ORD record
ord-7fe182389dc54e1787f7ef9ba8229532
Source dataset
uspto-grants-2007_03
Patent number
US07192946B2

Reaction notes

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