Sodium Carbonate → 1,1-Dioxo-3-butyl-3-ethyl-5-phenyl-7-bromo-8-[1'-phenyl-1'-ethoxycarbonylmethoxy]-2,3,4,5-tetrahydro-1,5-benzothiazepine

HRID 458908Notes

Reaction equation

HRID 458908 reaction equation
Br[CH:2]([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:3]([O:5][CH2:6][CH3:7])=[O:4].C([O-])([O-])=O.[Na+].[Na+].[O:20]=[S:21]1(=[O:46])[C:27]2[CH:28]=[C:29]([OH:33])[C:30]([Br:32])=[CH:31][C:26]=2[N:25]([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[CH2:24][C:23]([CH2:42][CH2:43][CH2:44][CH3:45])([CH2:40][CH3:41])[CH2:22]1>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.CC#N>[O:46]=[S:21]1(=[O:20])[C:27]2[CH:28]=[C:29]([O:33][CH:2]([C:8]3[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=3)[C:3]([O:5][CH2:6][CH3:7])=[O:4])[C:30]([Br:32])=[CH:31][C:26]=2[N:25]([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[CH2:24][C:23]([CH2:42][CH2:43][CH2:44][CH3:45])([CH2:40][CH3:41])[CH2:22]1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 97780Ethyl bromophenylacetateHCID 98250801,1-Dioxo-3-butyl-3-ethyl-5-phenyl-7-bromo-8-hydroxy-2,3,4,5-tetrahydro-1,5-benzothiazepine

Product 1

HCID 184424591,1-Dioxo-3-butyl-3-ethyl-5-phenyl-7-bromo-8-[1'-phenyl-1'-ethoxycarbonylmethoxy]-2,3,4,5-tetrahydro-1,5-benzothiazepineYield 94.2%

Reagents, catalysts & solvents 2

HCID 74236Tetrabutylammonium BromideCatalystHCID 6342AcetonitrileSolvent

Procedure

Ethyl α-bromophenylacetate (0.139 g), Na2CO3 (0.200 g) and tetrabutylammonium bromide (0.034 g) were 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; 0.200 g, 0.442 mmol) in MeCN (6 ml). The suspension was heated under reflux overnight before the solvent was removed under reduced pressure. The crude product was extracted (DCM/H2O) and purified by flash chromatography (Hex:EtOAc-5:1) to give the title compound 0.256 g (94%) as a white solid. NMR 0.65–0.85 (m, 6H), 0.95–1.65 (m, 8H), 3.00–3.15 (m, 2H), 3.50–3.80 (m, 2H), 3.70–3.80 (2s, 3H), 5.60 (s, 1H), 5.65 (d, 1H) 7.00–7.60 (m, 17H), 8.05–8.20 (2d, 1H).

Workup

  1. temperatureThe suspension was heated
  2. temperatureunder reflux overnight before the solvent
  3. customwas removed under reduced pressure
  4. extractionThe crude product was extracted (DCM/H2O)
  5. custompurified by flash chromatography (Hex:EtOAc-5:1)

Sources & evidence

ORD record
ord-9e4f61d2237d45b4808f70a51e5bd1d7
Source dataset
uspto-grants-2007_03
Patent number
US07192945B2

Reaction notes

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