3,4-dihydro-2H-pyran → HCID 90409410, compound

HRID 1855094Notes

Reaction equation

HRID 1855094 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([F:10])[C:5]([F:9])=[C:6]([OH:8])[CH:7]=1.[O:11]1[CH:16]=[CH:15][CH2:14][CH2:13][CH2:12]1>C(Cl)Cl.CC1C=CC(S([O-])(=O)=O)=CC=1.C1C=C[NH+]=CC=1>[Br:1][C:2]1[CH:3]=[C:4]([F:10])[C:5]([F:9])=[C:6]([CH:7]=1)[O:8][CH:12]1[CH2:13][CH2:14][CH2:15][CH2:16][O:11]1

Participants

5

Reactant 2

HCID 80803,4-dihydro-2H-pyranHCID 27733075-Bromo-2,3-Difluorophenol

Product 1

HCID 90409410HCID 90409410, compoundYield 65%

Reagents, catalysts & solvents 2

HCID 466102Benzenesulfonic acid, 4-methyl-, compd. with pyridine (1:1)CatalystHCID 6344DichloromethaneSolvent

Procedure

A solution of 5-bromo-2,3-difluorophenol (2.75 g, 13.16 mmol), 3,4-dihydro-2H-pyran (2.39 mL, 26.3 mmol) and PPTS (0.165 g, 0.658 mmol) in DCM (10 mL) was stirred for 1 h at rt. At this time, analytical HPLC showed that the reaction was complete. The reaction was concentrated in vacuo. The crude oily product was chromatographed [SiO2; continuous gradient of EtOAc/hexane (0% to 20% over 15 min)] to give the title compound (2.5 g, 8.5 mmol, 65% yield) as a clear oil. 1H NMR (CDCl3) δ: 7.17 (dt, J=6.4, 2.2 Hz, 1H), 6.99 (ddd, J=8.8, 6.2, 2.4 Hz, 1H), 5.45 (t, J=3.0 Hz, 1H), 3.88 (td, J=11.0, 3.0 Hz, 1H), 3.72-3.62 (m, 1H), 2.11-1.82 (m, 3H), 1.80-1.59 (m, 3H); 19F NMR (CDCl3) δ: −135.00, −158.84.

Workup

  1. concentrationThe reaction was concentrated in vacuo
  2. customThe crude oily product was chromatographed [SiO2; continuous gradient of EtOAc/hexane (0% to 20% over 15 min)]

Sources & evidence

ORD record
ord-9b7e36eb716542958019873a52fc4b87
Source dataset
uspto-grants-2015_02
Patent number
US08962660B2

Reaction notes

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