Ethylene Glycol → 3-[2-(2-Benzyloxy-ethyl)-[1,3]dioxolan-2-ylmethyl]-4-(4-chloro-benzenesulfonyl)-5,8-difluoro-chroman

HRID 564322Notes

Reaction equation

HRID 564322 reaction equation
[CH2:1]([O:8][CH2:9][CH2:10][C:11](=[O:35])[CH2:12][CH:13]1[CH:22]([S:23]([C:26]2[CH:31]=[CH:30][C:29]([Cl:32])=[CH:28][CH:27]=2)(=[O:25])=[O:24])[C:21]2[C:16](=[C:17]([F:34])[CH:18]=[CH:19][C:20]=2[F:33])[O:15][CH2:14]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:36](O)[CH2:37][OH:38].C1(C)C(S(O)(=O)=O)=CC=CC=1.O>C1(C)C=CC=CC=1.C(OCC)(=O)C>[CH2:1]([O:8][CH2:9][CH2:10][C:11]1([CH2:12][CH:13]2[CH:22]([S:23]([C:26]3[CH:27]=[CH:28][C:29]([Cl:32])=[CH:30][CH:31]=3)(=[O:25])=[O:24])[C:21]3[C:16](=[C:17]([F:34])[CH:18]=[CH:19][C:20]=3[F:33])[O:15][CH2:14]2)[O:38][CH2:37][CH2:36][O:35]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 174Ethylene GlycolHCID 962WaterHCID 69252-Methylbenzenesulfonic acidHCID 670063444-Benzyloxy-1-[4-(4-chloro-benzenesulfonyl)-5,8-difluoro-chroman-3-yl]-butan-2-one

Product 1

HCID 670057693-[2-(2-Benzyloxy-ethyl)-[1,3]dioxolan-2-ylmethyl]-4-(4-chloro-benzenesulfonyl)-5,8-difluoro-chroman

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

4-Benzyloxy-1-[4-(4-chloro-benzenesulfonyl)-5,8-difluoro-chroman-3-yl]-butan-2-one (10 g, 19.2 mmole), ethylene glycol (20 ml) and toluene sulfonic acid (1 g) were dissolved in 300 ml toluene. The reaction was refluxed for four hours with a Dean-Stark trap. The reaction was cooled to room temperature and 200 ml water and 200 ml EtOAc were added. The organic layer washed with brine (2×50 ml), dried over Na2SO4 and concentrated. The residue was purified by column chromatography (EtOAc/hexane from 0/100 to 50/50 in 55 minute). Yield: 6.3 g, 58%. 1H NMR (CDCl3 400 MHz δ 7.74 (d, J=8.1 Hz, 2H), 7.51 (d, J=8.8 Hz, 2H), 7.20-7.39 (m, 5H), 7.02 (m, 1H), 6.42 (m, 1H), 4.89 (dd, J=11.0 and 2.9 Hz, 1H), 4.84 (s, 1H), 4.40 (d, J=2.0 Hz, 2H), 4.21 (d, J=11.7 Hz, 1H), 3.85 (m, 4H), 3.46 (t, J=5.9 Hz, 2H), 3.03 (d, J=8.1 Hz, 1H), 1.75-1.90 (m, 3H), 1.54-1.61 (m, 1H).

Workup

  1. temperatureThe reaction was refluxed for four hours with a Dean-Stark trap
  2. washThe organic layer washed with brine (2×50 ml)
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated
  5. customThe residue was purified by column chromatography (EtOAc/hexane from 0/100 to 50/50 in 55 minute)

Sources & evidence

ORD record
ord-a5478cc3b3cb465a9d6e49eebf9bc368
Source dataset
uspto-grants-2011_11
Patent number
US08067621B2

Reaction notes

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