Epichlorohydrin → HCID 58150208, compound

HRID 410136Notes

Reaction equation

HRID 410136 reaction equation
ClC1[CH:7]=[CH:6][C:5]([CH:8]([S:17](C(C2C=CC(Cl)=CC=2)C2C=C(F)C=CC=2F)(=[O:19])=[O:18])[C:9]2[CH:14]=[C:13]([F:15])[CH:12]=[CH:11][C:10]=2[F:16])=CC=1.[Li][CH2:37][CH2:38][CH2:39]C.[CH2:41]([CH:43]1O[CH2:44]1)[Cl:42].C1C[O:49]CC1>>[Cl:42][C:41]1[CH:39]=[CH:38][C:37]([S:17]([CH:8]([C:9]2[CH:14]=[C:13]([F:15])[CH:12]=[CH:11][C:10]=2[F:16])[CH2:5][CH:6]2[CH2:7][O:49]2)(=[O:19])=[O:18])=[CH:44][CH:43]=1

Participants

5

Reactant 4

HCID 7835EpichlorohydrinHCID 8028TetrahydrofuranHCID 87194351HCID 87194351, compoundHCID 178418339Butyllithium

Product 1

HCID 58150208HCID 58150208, compound

Procedure

4-chlorophenyl-2,5-difluorobenzylsulfone (12 g, 39.6 mmol) in THF (99 ml) was treated with nBuLi (19 ml, 2.5 M in hexane, 47.6 mmol) at 0° C. for 10 min followed by addition of epichlorohydrin (3.73 ml, 47.6 mmol). The reaction was slowly warmed to room temperature for 14 h, quenched with water (100 ml) and diluted with EtOAc (300 ml). The organic phase was separated, dried (Na2SO4) and evaporated to dryness to give an oil. This material was chromatographed on silica, eluting with 10-45% ethyl acetate in hexanes to afford 9.8 g of the desired product as off-white solid. 1H NMR (600 MHZ, CDCl3) two diastereomers (˜1/1) δ 7.52 (m, 2H/2H), 7.38 (m, 2H/2H), 7.30-7.22 (m, 1H/1H), 6.99 (m, 1H/1H), 6.86-6.80 (m, 1H/1H), 4.76-4.70 (m, 1H/1H), 3.03-2.48 (m, 4H/4H), 2.37 (m, 1H), 2.20 (m, 1H). MS calculated 359.0 (MH+), exp 358.9 (MH+).

Workup

  1. customquenched with water (100 ml)
  2. additiondiluted with EtOAc (300 ml)
  3. customThe organic phase was separated
  4. dry with materialdried (Na2SO4)
  5. customevaporated to dryness
  6. customto give an oil
  7. customThis material was chromatographed on silica
  8. washeluting with 10-45% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-084671ef914540679e694b45ae5a61a3
Source dataset
uspto-grants-2014_06
Patent number
US08759579B2

Reaction notes

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