Sodium borohydride → HCID 18442442, compound

HRID 458514Notes

Reaction equation

HRID 458514 reaction equation
[O:1]=[S:2]1(=[O:30])[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]([CH2:26][CH2:27][CH2:28][CH3:29])([CH2:22][CH2:23][CH2:24][CH3:25])[CH2:3]1.[CH3:31][S-:32].[Na+].[BH4-].[Na+].Cl[O-].[Na+]>CCOC(C)=O.O.C(O)(=O)C.CN(C=O)C>[O:30]=[S:2]1(=[O:1])[C:8]2[CH:9]=[C:10]([OH:14])[C:11]([S:32][CH3:31])=[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]([CH2:22][CH2:23][CH2:24][CH3:25])([CH2:26][CH2:27][CH2:28][CH3:29])[CH2:3]1

Participants

9

Reactant 4

HCID 4311764Sodium borohydride2×HCID 4378561Sodium methanethiolate2×HCID 18442439HCID 18442439, compoundHCID 23665760Sodium Hypochlorite

Product 1

HCID 18442442HCID 18442442, compoundYield 93%

Reagents, catalysts & solvents 4

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

To 1,1-dioxo-3,3-dibutyl-5-phenyl-7-bromo-8-methoxy-2,3,4,5-tetrahydro-1,5-benzothiazepine (synthesised by the of WO9616051 for the corresponding 3-butyl-3-ethyl analogue; 40 mg, 0.08 mmol) was added DMF (2 ml), sodium methanethiolate (60 mg, 0.85 mmol) and sodium borohydride (60 mg, 1.6 mmol). The reaction was run overnight at 60° C. Additional sodium borohydride (60 mg, 1.6 mmol) and sodium methanethiolate (60 mg, 0.85 mmol) was added and the temperature was raised to 120° C. The reaction heated at this temperature for 4 hours and then cooled to room temperature. Then acetic acid was added under a flow of nitrogen, through sodium hypochlorite overnight. Water and EtOAc was added and the aqueous phase was extracted three times with EtOAc. The combined organic phases were washed with HCl (1M), dried and concentrated under reduced pressure. The residue was then purified by flash chromatography [EtOAc: heptane, 1:4] to give the title compound 0.34 g (93%). NMR 0.7–0.9 (m, 6H), 1.0–1.6 (m, 12H), 2.2 (s, 3H), 3.1(s, 2H), 3.4 (s, 2H), 3.7 (brs, 2H), 6.7 (s, 1H), 6.85–7.05 (m, 2H), 7.2–7.4 (m, 2H).

Workup

  1. temperatureThe reaction heated at this temperature for 4 hours
  2. temperaturecooled to room temperature
  3. extractionthe aqueous phase was extracted three times with EtOAc
  4. washThe combined organic phases were washed with HCl (1M)
  5. customdried
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was then purified by flash chromatography [EtOAc: heptane, 1:4]

Sources & evidence

ORD record
ord-d2ea23f5356e4d539e6483ef7ceb3ccb
Source dataset
uspto-grants-2007_03
Patent number
US07192947B2

Reaction notes

Loading…