Acetic Acid → HCID 86727211, compound

HRID 2274320Notes

Reaction equation

HRID 2274320 reaction equation
[CH2:1]([O:8][C@@H:9]1[C@H:14]2[N:15]=[C:16]([N:18]([CH3:20])[CH3:19])[S:17][C@H:13]2[CH2:12][C@H:11]([CH2:21][O:22]CC2C=CC=CC=2)[C@H:10]1[O:30][CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([O-])([O-])=O.[K+].[K+].CC(O)=O>CC(OC(C)=O)=O.CC(O)=O.[Cl-].[Cl-].[Zn+2]>[CH2:1]([O:8][C@@H:9]1[C@H:14]2[N:15]=[C:16]([N:18]([CH3:20])[CH3:19])[S:17][C@H:13]2[CH2:12][C@H:11]([CH2:21][OH:22])[C@H:10]1[O:30][CH2:31][C:32]1[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 176Acetic AcidHCID 11430Potassium CarbonateHCID 71258140HCID 71258140, compound

Product 1

HCID 86727211HCID 86727211, compoundYield 46%

Reagents, catalysts & solvents 2

HCID 3007855ZincchlorideCatalystHCID 21895370AcOH AcOAcSolvent

Procedure

At 15° C., to a solution of (3aR,4R,5R,6R,7aS)-4,5-bis(benzyloxy)-6-((benzyloxy)methyl)-N,N-dimethyl-3a,4,5,6,7,7a-hexahydrobenzo[d]thiazol-2-amine (13) (0.950 g, 1.84 mmol) in mixed Ac2O/AcOH (10 mL/2 mL) was added anhydrous ZnCl2 (2.5 g, 18 mmol). The mixture was stirred at room temperature for 2 h and concentrated under vacuum at room temperature. The residue was diluted with DCM (50 mL) and saturated aqueous NaHCO3 (50 mL). The mixture was stirred for 30 min, and the solid was filtered off over a Celite 521 cake. The organic layer was collected from the filtrate, and the aqueous was extracted with DCM (3×30 mL). The combined extract was dried over anhydrous Na2SO4. After filtration the solvent was evaporated under reduced pressure, and the residue was dissolved in MeOH (15 mL). Anhydrous K2CO3 (0.47 g, 3.4 mmol) was added, and the mixture was stirred at room temperature for 2 h. AcOH (0.5 mL) was added and the reaction mixture was concentrated under reduced pressure at room temperature. The residue was diluted with saturated aqueous NaHCO3 (30 mL), and then extracted with DCM (3×30 mL). The combined extract was dried over anhydrous Na2SO4. After filtration the solvent was evaporated under reduced pressure, and the residue was purified on silica gel by flash column chromatography (EtOAc, then MeOH/DCM, 1:10), affording 14 as a sticky pale yellow foam (0.36 g, 46%). 1H NMR (400 MHz, CDCl3) δ 7.44-7.41 (m, 2H), 7.36-7.24 (m, 8H), 5.02 (d, J=11.0 Hz, 1H), 4.95 (d, J=11.2 Hz, 1H), 4.70 (d, J=11.0 Hz, 1H), 4.62 (d, J=11.2 Hz, 1H), 4.31-4.28 (m, 1H), 4.11 (t, J=7.3 Hz, 1H), 3.70 (t, J=8.4 Hz, 1H), 3.64-3.62 (m, 2H), 3.35 (dd, J=8.9, 10.2 Hz, 1H), 3.00 (s, 6H), 2.23 (s, br. 1H), 2.24-2.16 (m, 1H), 2.07-2.02 (m, 1H), 1.72-1.64 (m, 1H).

Workup

  1. concentrationconcentrated under vacuum at room temperature
  2. additionThe residue was diluted with DCM (50 mL) and saturated aqueous NaHCO3 (50 mL)
  3. stirringThe mixture was stirred for 30 min
  4. filtrationthe solid was filtered off over a Celite 521 cake
  5. customThe organic layer was collected from the filtrate
  6. extractionthe aqueous was extracted with DCM (3×30 mL)
  7. extractionThe combined extract
  8. dry with materialwas dried over anhydrous Na2SO4
  9. filtrationAfter filtration the solvent
  10. customwas evaporated under reduced pressure
  11. dissolutionthe residue was dissolved in MeOH (15 mL)
  12. stirringthe mixture was stirred at room temperature for 2 h
  13. concentrationthe reaction mixture was concentrated under reduced pressure at room temperature
  14. additionThe residue was diluted with saturated aqueous NaHCO3 (30 mL)
  15. extractionextracted with DCM (3×30 mL)
  16. extractionThe combined extract
  17. dry with materialwas dried over anhydrous Na2SO4
  18. filtrationAfter filtration the solvent
  19. customwas evaporated under reduced pressure
  20. customthe residue was purified on silica gel by flash column chromatography (EtOAc

Sources & evidence

ORD record
ord-9b13b38244f241c48b9b00b4e1d5b3e7
Source dataset
uspto-grants-2015_09
Patent number
US09126957B2

Reaction notes

Loading…