Dimethylformamide → HCID 22393104, compound

HRID 458922Notes

Reaction equation

HRID 458922 reaction equation
[O:1]=[S:2]1(=[O:28])[C:8]2[CH:9]=[C:10]([O:14]C)[C:11](Br)=[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]([CH2:24][CH2:25][CH2:26][CH3:27])([CH2:22][CH3:23])[CH2:3]1.CN(C=O)C.[CH3:34][S-:35].[Na+].Cl[O-].[Na+]>CCOC(C)=O.O.C(O)(=O)C>[O:1]=[S:2]1(=[O:28])[C:8]2[CH:9]=[C:10]([OH:14])[C:11]([S:35][CH3:34])=[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]([CH2:24][CH2:25][CH2:26][CH3:27])([CH2:22][CH3:23])[CH2:3]1

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 4378561Sodium methanethiolateHCID 22393116HCID 22393116, compoundHCID 23665760Sodium Hypochlorite

Product 1

HCID 22393104HCID 22393104, compoundYield 92.4%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

To 1,1-dioxo-3-butyl-3-ethyl-5-phenyl-7-bromo-8-methoxy-2,3,4,5-tetrahydro-1,5-benzothiazepine (WO9616051; 600 mg, 1.29 mmol) were added DMF (5 ml) and sodium methanethiolate (450 mg, 6.42 mmol). The reaction was then heated to 60° C. for 1 hour. The oil bath was then heated to 120° C. for 4 hours. To quench the reaction, the temperature was lowered to room temperature and excess acetic acid was added quickly. The reaction was kept under a flow of nitrogen through sodium hypochlorite for 2 hours. Water and EtOAc were added and the aqueous phase was extracted three times with EtOAc. The combined organic phases were washed with water, dried and concentrated under reduced pressure. The residue was then purified by flash chromatography [DCM:EtOAc, 9:1] to give the title compound 0.5 g (92%). NMR 0.65–0.8 (m, 6H), 0.95–1.6 (m, 8h), 3.1 (q, 2H), 3.6 (brq, 2H), 6.75 (s, 1H), 6.8 (t, 1H), 6.9 (d, 2H), 7.15 (t, 2H), 7.55 (s, 1H).

Workup

  1. temperatureThe oil bath was then heated to 120° C. for 4 hours
  2. customTo quench
  3. customthe reaction
  4. customwas lowered to room temperature
  5. extractionthe aqueous phase was extracted three times with EtOAc
  6. washThe combined organic phases were washed with water
  7. customdried
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was then purified by flash chromatography [DCM:EtOAc, 9:1]

Sources & evidence

ORD record
ord-662880608f52478c98dc1d8789483d70
Source dataset
uspto-grants-2007_03
Patent number
US07192945B2

Reaction notes

Loading…