Ethylene Glycol → HCID 86722340, compound

HRID 718761Notes

Reaction equation

HRID 718761 reaction equation
[CH2:1]([C@@:3]12[CH2:13][CH2:12][C:11](=[O:14])[CH2:10][C@@H:9]1[CH2:8][CH2:7][CH2:6][C:5]1[CH:15]=[C:16]([O:19][S:20]([C:23]([F:26])([F:25])[F:24])(=[O:22])=[O:21])[CH:17]=[CH:18][C:4]2=1)[CH3:2].C([C@]12CC[C:37](=[O:40])[CH2:36][C@H]1CCCC1C=C(OS(C(F)(F)F)(=O)=O)C=CC2=1)C.C(O)CO.CC1C=CC(S(O)(=O)=O)=CC=1.C([O-])(O)=O.[Na+]>CCOC(C)=O.C1(C)C=CC=CC=1>[F:25][C:23]([F:26])([F:24])[S:20]([O:19][C:16]1[CH:17]=[CH:18][C:4]2[C:3]3([CH2:1][CH3:2])[CH2:13][CH2:12][C:11]4([O:40][CH2:37][CH2:36][O:14]4)[CH2:10][CH:9]3[CH2:8][CH2:7][CH2:6][C:5]=2[CH:15]=1)(=[O:21])=[O:22]

Participants

7

Reactant 4

HCID 174Ethylene GlycolHCID 6101p-Toluenesulfonic acidHCID 516892Sodium BicarbonateHCID 86671178HCID 86671178, compound

Product 1

HCID 86722340HCID 86722340, compoundYield 90%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A flask equipped with a Dean-Stark apparatus was charged with trifluoro-methanesulfonic acid (7aR,11aS)-11a-ethyl-9-oxo-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cyclohepten-3-yl ester; compound with trifluoro-methanesulfonic acid (7 aS,11aR)-11a-ethyl-9-oxo-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cyclohepten-3-yl ester (19, R2=Ethyl) (2.2 g, 5.63 mmol), ethane-1,2-diol (1.571 mL, 28.2 mmol), pTSA (0.107 g, 0.563 mmol) and toluene (44 mL). The mixture was heated to reflux for about 21 h. The mixture was cooled to rt, EtOAc (20 mL), sat. aq. NaHCO3 (10 mL) were added and the layers were separated. The organic layer was washed with brine (15 mL), dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified on silica gel (12 g) using a gradient of 0-40% EtOAc in heptane. Product fractions were combined and concentrated under reduced pressure to yield rac-(4aR,11bS)-11b-ethyl-1,2,4,4a,5,6,7,11b-octahydrospiro[dibenzo[a,c][7]annulene-3,2′-[1,3]dioxolan]-9-yl trifluoromethanesulfonate (20, R2=Ethyl) (2.2 g, 90%); LC/MS, method 3, Rt=3.05 min, MS m/z 435 (M+H)+. 1H NMR (400 MHz, DMSO) δ 7.42-7.35 (m, 1H), 7.26-7.22 (m, 2H), 3.91-3.69 (m, 4H), 3.04-2.77 (m, 2H), 2.43-2.37 (m, 1H), 2.22-2.13 (m, 1H), 2.11-1.94 (m, 2H), 1.71-1.62 (m, 2H), 1.61-1.54 (m, 2H), 1.52-1.35 (m, 3H), 1.32-1.17 (m, 2H), 0.59 (t, J=7.4 Hz, 3H).

Workup

  1. customA flask equipped with a Dean-Stark apparatus
  2. temperatureThe mixture was heated
  3. temperatureto reflux for about 21 h
  4. customthe layers were separated
  5. washThe organic layer was washed with brine (15 mL)
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified on silica gel (12 g)
  10. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-a4d442dd94f245f98986f9ff65b8e370
Source dataset
uspto-grants-2015_11
Patent number
US09193744B2

Reaction notes

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