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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 458906
Notes
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Reaction equation

HRID 458906 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
ParticipantsProcedureWorkupSources & evidenceReaction notes

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 74236
Tetrabutylammonium Bromide
Catalyst
HCID 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 overnight. 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. NMR 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 overnight
  3. customThe solvent was evaporated
  4. extractionthe crude mixture was extracted (DCM/H2O)
  5. customdried
  6. custom(MgSO4), evaporated
  7. custompurified by flash chromatography (Hex:EtOAc-5:1)

Sources & evidence

ORD record
ord-2f8d0839e8044f61b8f36d00c63bee07
Source dataset
uspto-grants-2007_03
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07192945B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes