Ethyl bromoacetate → HCID 22393110, compound

HRID 1071302Notes

Reaction equation

HRID 1071302 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 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-06fa19dbe6574052baf31fb6937e048f
Source dataset
uspto-grants-2005_06
Patent number
US06906058B2

Reaction notes

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