Ethyl bromoacetate → HCID 18442453, compound

HRID 458946Notes

Reaction equation

HRID 458946 reaction equation
[O:1]=[S:2]1(=[O:28])[C:8]2[CH:9]=[C:10]([OH:15])[C:11]([S:13][CH3:14])=[CH:12][C:7]=2[N:6]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH2:5][C:4]([CH2:25][CH2:26][CH3:27])([CH2:22][CH2:23][CH3:24])[CH2:3]1.Br[CH2:30][C:31]([O:33]CC)=[O:32].C(=O)([O-])[O-].[Na+].[Na+].[OH-].[Na+]>CC#N.[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.O>[O:28]=[S:2]1(=[O:1])[C:8]2[CH:9]=[C:10]([O:15][CH2:30][C:31]([OH:33])=[O:32])[C:11]([S:13][CH3:14])=[CH:12][C:7]=2[N:6]([C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH2:5][C:4]([CH2:25][CH2:26][CH3:27])([CH2:22][CH2:23][CH3:24])[CH2:3]1

Participants

8

Reactant 4

HCID 7748Ethyl bromoacetateHCID 10340Sodium CarbonateHCID 14798Sodium HydroxideHCID 18442454HCID 18442454, compound

Product 1

HCID 18442453HCID 18442453, compound

Reagents, catalysts & solvents 3

HCID 74236Tetrabutylammonium BromideCatalystHCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

To a suspension of 1,1-dioxo-3,3-dipropyl-5-phenyl-7-methylthio-8-hydroxy-2,3,4,5-tetrahydro-1,5-benzothiazepine (Method 117; 0.665 g, 1.58 mmol) in MeCN (10 ml) was added ethyl bromoacetate (0.262 ml, 2.35 mmol), tetrabutylammonium bromide (0.051 g, 0.158 mmol) and sodium carbonate (0.870 g, 8.21 mmol). The mixture was stirred over night at 80° C. The solvent was removed under reduced pressure and the residue was partitioned between EtOAc and 0.5 M HCl. The organic layer was washed with brine, dried (MgSO4) and concentrated. The residue was filtered through a short silica column (DCM:EtOAc-9:1), concentrated and dissolved in EtOH (10 ml). A solution of NaOH (0.25 g, 6.25 mmol) in water (1 ml) was added and the solution was stirred over night at room temperature. The solvent was removed under reduced pressure and the residue was partitioned between EtOAc and 0.5 M HCl. The aqueous layer was extracted twice more with EtOAc and the combined organic extracts were washed with brine and concentrated. The crude product was purified by preparative HPLC using a MeCN/ammonium acetate buffer to give the title compound in 0.441 g (58%) as a white solid. NMR (DMSO-d6) 0.55–0.75 (m; 6H), 1.05–1.50 (m, 8H), 2.15 (s, 3H), 3.20 (s, 2H), 3.65 (brs, 2H), 4.50 (s, 2H), 6.65 (s, 1H), 6.80–7.00 (m, 3H), 7.15 (s, 1H), 7.15–7.25 (m, 2H).

Workup

  1. customThe solvent was removed under reduced pressure
  2. customthe residue was partitioned between EtOAc and 0.5 M HCl
  3. washThe organic layer was washed with brine
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated
  6. filtrationThe residue was filtered through a short silica column (DCM:EtOAc-9:1)
  7. concentrationconcentrated
  8. dissolutiondissolved in EtOH (10 ml)
  9. stirringthe solution was stirred over night at room temperature
  10. customThe solvent was removed under reduced pressure
  11. customthe residue was partitioned between EtOAc and 0.5 M HCl
  12. extractionThe aqueous layer was extracted twice more with EtOAc
  13. washthe combined organic extracts were washed with brine
  14. concentrationconcentrated
  15. customThe crude product was purified by preparative HPLC

Sources & evidence

ORD record
ord-9bfee5b72f494d61b6967404b7565748
Source dataset
uspto-grants-2007_03
Patent number
US07192945B2

Reaction notes

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