Sodium Carbonate → 1,1-Dioxo-3-butyl-3-ethyl-5-phenyl-7-bromo-8-(1-ethoxycarbonylethoxy)-2,3,4,5-tetrahydro-1,5-benzothiazepine

HRID 1071300Notes

Reaction equation

HRID 1071300 reaction equation
C(=O)([O-])[O-].[Na+].[Na+].[CH2:7]([O:9][C:10](=[O:14])[CH:11](Br)[CH3:12])[CH3:8].[O:15]=[S:16]1(=[O:41])[C:22]2[CH:23]=[C:24]([OH:28])[C:25]([Br:27])=[CH:26][C:21]=2[N:20]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[CH2:19][C:18]([CH2:37][CH2:38][CH2:39][CH3:40])([CH2:35][CH3:36])[CH2:17]1>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.CC#N>[O:41]=[S:16]1(=[O:15])[C:22]2[CH:23]=[C:24]([O:28][CH:11]([C:10]([O:9][CH2:7][CH3:8])=[O:14])[CH3:12])[C:25]([Br:27])=[CH:26][C:21]=2[N:20]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[CH2:19][C:18]([CH2:37][CH2:38][CH2:39][CH3:40])([CH2:35][CH3:36])[CH2:17]1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 79040Ethyl 2-bromopropionateHCID 98250801,1-Dioxo-3-butyl-3-ethyl-5-phenyl-7-bromo-8-hydroxy-2,3,4,5-tetrahydro-1,5-benzothiazepine

Product 1

HCID 223931141,1-Dioxo-3-butyl-3-ethyl-5-phenyl-7-bromo-8-(1-ethoxycarbonylethoxy)-2,3,4,5-tetrahydro-1,5-benzothiazepineYield 95%

Reagents, catalysts & solvents 2

HCID 74236Tetrabutylammonium BromideCatalystHCID 6342AcetonitrileSolvent

Procedure

Sodium carbonate (0.30 g, 2.83 mmol), 2-bromopropanoic acid ethyl ester (0.145 g, 0.796 mmol) and tetrabutylammonium bromide (0.022 g, 0.07 mmol) was added to a solution 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; 0.300 g, 0.663 mmol) in MeCN (10 ml). The suspension was heated under reflux over night. The solvent was evaporated and the crude mixture was extracted (DCM/H2O), dried (MgSO4), evaporated and purified by flash chromatography (Hex:EtOAc-5:1) to give the title compound 0.346 g (95%) as a white solid. NM (400 MHz) 0.70-0.85 (m, 6H), 1.00-1.75 (m, 8H), 1.35 (t, 3H), 1.70 (d, 3H), 3.05-3.25 (m, 2H), 3.55-3.90 (m, 2H), 4.20-4.35 (m, 2H), 4.80 (q, 1H), 7.00-7.10 (m, 3H), 7.15 (s, 1H), 7.25-7.35 (m, 2H), 7.45 (s, 1H).

Workup

  1. temperatureThe suspension was heated
  2. temperatureunder reflux over night
  3. customThe solvent was evaporated
  4. extractionthe crude mixture was extracted (DCM/H2O)
  5. dry with materialdried (MgSO4)
  6. customevaporated
  7. custompurified by flash chromatography (Hex:EtOAc-5:1)

Sources & evidence

ORD record
ord-39ba3497c10748cc95889c1cfe0853ca
Source dataset
uspto-grants-2005_06
Patent number
US06906058B2

Reaction notes

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