Sodium hydride → 2-[3-(2,4-Difluorophenyl)sulfanylpropoxy]oxane

HRID 600548Notes

Reaction equation

HRID 600548 reaction equation
[H-].[Na+].[F:3][C:4]1[CH:9]=[C:8]([F:10])[CH:7]=[CH:6][C:5]=1[SH:11].Br[CH2:13][CH2:14][CH2:15][O:16][CH:17]1[CH2:22][CH2:21][CH2:20][CH2:19][O:18]1>C1COCC1>[F:3][C:4]1[CH:9]=[C:8]([F:10])[CH:7]=[CH:6][C:5]=1[S:11][CH2:13][CH2:14][CH2:15][O:16][CH:17]1[CH2:22][CH2:21][CH2:20][CH2:19][O:18]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 27370732,4-Difluorobenzene-1-thiolHCID 27779882-(3-Bromopropoxy)tetrahydro-2H-pyran

Product 1

HCID 576632252-[3-(2,4-Difluorophenyl)sulfanylpropoxy]oxaneYield 84%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Sodium hydride (60%) (1.72 g, 44.8 mmol) was added to a solution of 2,4-difluorobenzenethiol (CAS no. 1996-44-7) (4.6 mL, 40 mmol) in THF (150 mL) at 0° C., under argon. The mixture was allowed to warm to room temperature and 2-(3-bromopropoxy)oxane (CAS no. 33821-94-2) (7.6 mL, 45 mmol) was added. The reaction was stirred at ambient temperature for 16 hours. The mixture was poured into ice/water (250 mL) and extracted with ethyl acetate (250 mL). The organic extract was washed with brine, dried (MgSO4) and the solvent removed under reduced pressure. The residue was purified by flash chromatography, eluting with 0-10% ethyl acetate in isohexane afford the product (10.8 g, 84%). 1H NMR δ(400 MHZ, CDCl3): 1.49-1.61 (m, 4H), 1.65-1.73 (m, 1H), 1.75-1.90 (m, 3H), 2.96 (t, 2H), 3.46-3.52 (m, 2H), 3.79-3.87 (m, 2H), 4.55-4.56 (m, 1H), 6.80-6.86 (m, 2H), 7.38-7.44 (m, 1H).

Workup

  1. customat 0° C.
  2. addition33821-94-2) (7.6 mL, 45 mmol) was added
  3. extractionextracted with ethyl acetate (250 mL)
  4. extractionThe organic extract
  5. washwas washed with brine
  6. dry with materialdried (MgSO4)
  7. customthe solvent removed under reduced pressure
  8. customThe residue was purified by flash chromatography
  9. washeluting with 0-10% ethyl acetate in isohexane

Sources & evidence

ORD record
ord-f131fa91eefe4c5081b3c63dc0d4ab5a
Source dataset
uspto-grants-2011_03
Patent number
US07902200B2

Reaction notes

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