Water → 3-(2-Benzyloxy-ethoxymethyl)-4-(4-chloro-phenylsulfanyl)-5,8-difluoro-chroman

HRID 564315Notes

Reaction equation

HRID 564315 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8][C@@H:9]2[C:18]3[C:13](=[C:14]([F:20])[CH:15]=[CH:16][C:17]=3[F:19])[O:12][CH2:11][C@H:10]2[CH2:21][OH:22])=[CH:4][CH:3]=1.Br[CH2:24][CH2:25][O:26][CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.[H-].[Na+].O>C1COCC1.C(OCC)(=O)C>[CH2:27]([O:26][CH2:25][CH2:24][O:22][CH2:21][CH:10]1[CH:9]([S:8][C:5]2[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=2)[C:18]2[C:13](=[C:14]([F:20])[CH:15]=[CH:16][C:17]=2[F:19])[O:12][CH2:11]1)[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1

Participants

7

Reactant 4

HCID 962WaterHCID 24758Sodium hydride2×HCID 73833Benzene, ((2-bromoethoxy)methyl)-2×HCID 58445368Trans-[4-(4-chloro-phenylsulfanyl)-5,8-difluoro-chroman-3-yl]-methanol

Product 1

HCID 670064253-(2-Benzyloxy-ethoxymethyl)-4-(4-chloro-phenylsulfanyl)-5,8-difluoro-chroman

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

Trans-[4-(4-chloro-phenylsulfanyl)-5,8-difluoro-chroman-3-yl]-methanol (0.6 g, 1.65 mmole) and (2-bromo-ethoxymethyl)-benzene (0.71 g, 3.3 mmole) were dissolved in 30 ml THF and NaH (0.5 g) was added. The reaction was stirred at room temperature overnight. (2-Bromo-ethoxymethyl)-benzene (0.71 g, 3.3 mmole) and NaH (0.5 g) were added and the reaction was refluxed overnight. 50 ml water and 50 ml EtOAc were added. The organic layer washed with Sat. NaCl solution (50 ml), dried over Na2SO4 and concentrated. The product was purified by column chromatography (EtOAc/Hex. from 0/100 to 25/75 in 40 minute). Yield: 0.42 g, 53%. 1H NMR (CDCl3 400 MHz δ 7.42 (d, J=8.8 Hz, 2H), 7.25-7.37 (m, 7H), 6.96 (m, 1H), 6.57 (m, 1H), 4.60 (dd, J=11.7 and 2.2 Hz, 1H), 4.52 (bs, 3H), 4.40 (t, J=11.0, 1H), 3.3-3.56 (m, 6H), 2.38 (m, 1H).

Workup

  1. temperaturethe reaction was refluxed overnight
  2. washThe organic layer washed with Sat. NaCl solution (50 ml)
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated
  5. customThe product was purified by column chromatography (EtOAc/Hex. from 0/100 to 25/75 in 40 minute)

Sources & evidence

ORD record
ord-8947aa1a6f1149098c8fd35b6b32daf2
Source dataset
uspto-grants-2011_11
Patent number
US08067621B2

Reaction notes

Loading…