Water → Trans-[4-(4-chloro-phenylsulfanyl)-5,8-difluoro-chroman-3-yl]-methanol

HRID 564314Notes

Reaction equation

[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8][CH:9]([C:15]2[C:20]([F:21])=[CH:19][CH:18]=[C:17]([F:22])[C:16]=2F)[CH:10]([CH2:13][OH:14])[CH2:11][OH:12])=[CH:4][CH:3]=1.[H-].[Na+].O.C(OCC)(=O)C>C1COCC1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8][C@@H:9]2[C:15]3[C:16](=[C:17]([F:22])[CH:18]=[CH:19][C:20]=3[F:21])[O:12][CH2:11][C@H:10]2[CH2:13][OH:14])=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 60 °C

Procedure

2-[(4-Chloro-phenylsulfanyl)-(2,3,6-trifluoro-phenyl)-methyl]-propane-1,3-diol (6.2 g, 14.8 mmole) was dissolved in 150 mL THF and NaH (60% in oil, 2 g) was added. The reaction was stirred at 60° C. for four hours. 300 mL of water and 400 mL of EtOAc were added. The organic layer washed with brine (100 mL), dried over Na2SO4 and concentrated. The product was purified by column chromatography (EtOAc/hexane from 0/100 to 50/50 in 45 minutes). Yield: 5.0 g, 85%. 1H NMR (CDCl3 400 MHz) δ 7.45 (d, J=8.1 Hz, 2H), 7.32 (d, J=8.1 Hz, 2H), 6.97 (m, 1H), 6.58 (m, 1H), 4.62 (dd, J=11.7 and 2.2 Hz, 1H), 4.50 (br, 1H), 4.43 (td, J=11.7 and 2.2 Hz, 1H), 3.67 (m, 1H), 3.48 (m, 1H), 2.25 (m, 1H), 1.50 (t, J=5.1 Hz, 1H).

Workup

washThe organic layer washed with brine (100 mL)
dry with materialdried over Na2SO4
concentrationconcentrated
customThe product was purified by column chromatography (EtOAc/hexane from 0/100 to 50/50 in 45 minutes)

Sources & evidence

ORD record: ord-05199f9b34154419b9ea6fdf7bde4c95
Source dataset: uspto-grants-2011_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08067621B2

Reaction notes

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