Water → HCID 86623967, compound

HRID 1045323Notes

Reaction equation

HRID 1045323 reaction equation
[F:1][C:2]1[CH:21]=[CH:20][C:5]2[CH2:6][C:7]3[CH:19]=[CH:18][CH:17]=[CH:16][C:8]=3[CH:9]3[CH2:13][CH:12]([CH2:14][OH:15])[O:11][CH:10]3[C:4]=2[CH:3]=1.C(N(CC)CC)C.[CH3:29][C:30]1[CH:35]=[CH:34][C:33]([S:36](Cl)(=[O:38])=[O:37])=[CH:32][CH:31]=1.[OH2:40]>C(Cl)Cl>[F:1][C:2]1[CH:21]=[CH:20][C:5]2[CH2:6][C:7]3[CH:19]=[CH:18][CH:17]=[CH:16][C:8]=3[CH:9]3[CH2:13][CH:12]([CH2:14][OH:15])[O:11][CH:10]3[C:4]=2[CH:3]=1.[CH3:29][C:30]1[CH:35]=[CH:34][C:33]([S:36]([O-:38])(=[O:37])=[O:40])=[CH:32][CH:31]=1

Participants

6

Reactant 4

HCID 962WaterHCID 73974-Toluenesulfonyl chlorideHCID 8471TriethylamineHCID 58846411HCID 58846411, compound

Product 1

HCID 86623967HCID 86623967, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

[2R-(2α, 3aα, 12bβ)]-11-fluoro-2-hydroxymethyl-3,3a,8,12b-tetrahydro-2H-dibenzo [3,4:6,7]cyclohepta[1,2-b]furan (4.1 g, 0.0144 mol) was dissolved in DCM (20 ml). Triethylamine (0.0173 mol) was added and the mixture was cooled on an ice-bath. A solution of 4-methyl-benzenesulfonyl chloride (0.0159 mol) in DCM (10 ml) was added over ±5 min. The mixture was stirred for 2 hours at 0° C. then allowed to warm to room temperature. The reaction mixture was stirred overnight at room temperature. Water (20 ml) was added. The layers were separated. The organic phase was stirred in a 10% aqueous potassium carbonate solution for one hour. The layers were separated. The organic layer was dried (MgSO4), filtered and the solvent evaporated. The residue was stirred in toluene (30 ml). A 10% aqueous potassium carbonate solution (30 ml) was added. The layers were separated. The organic layer was dried (MgSO4), filtered and the solvent evaporated, yielding 5.8 g (92%) of [2R-(2α, 3aα, 12bβ)]11-fluoro-3,3a,8,12b-tetrahydro-2H-dibenzo[3,4:6,7]cyclohepta[1,2-b]furan-2-methanol-4-methylbenzenesulfonate, intermediate 1. An alternative method of preparing this intermediate is described in W003/048146 [CAS number=543741-40-8].

Workup

  1. temperaturethe mixture was cooled on an ice-bath
  2. temperatureto warm to room temperature
  3. stirringThe reaction mixture was stirred overnight at room temperature
  4. customThe layers were separated
  5. stirringThe organic phase was stirred in a 10% aqueous potassium carbonate solution for one hour
  6. customThe layers were separated
  7. dry with materialThe organic layer was dried (MgSO4)
  8. filtrationfiltered
  9. customthe solvent evaporated
  10. stirringThe residue was stirred in toluene (30 ml)
  11. additionA 10% aqueous potassium carbonate solution (30 ml) was added
  12. customThe layers were separated
  13. dry with materialThe organic layer was dried (MgSO4)
  14. filtrationfiltered
  15. customthe solvent evaporated

Sources & evidence

ORD record
ord-04de9012623249e5a578bfa6fc72a79e
Source dataset
uspto-grants-2013_10
Patent number
US08569267B2

Reaction notes

Loading…