Tetrahydrofuran → HCID 67056229, compound

HRID 1967434Notes

Reaction equation

HRID 1967434 reaction equation
[O:1]1[CH2:5][CH2:4][O:3][CH:2]1[C:6]1[CH:11]=[C:10]([O:12][CH3:13])[CH:9]=[CH:8][C:7]=1/[CH:14]=[CH:15]/[C:16]([N:18]1[C@H:22]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH2:21][O:20][C:19]1=[O:29])=[O:17].[CH2:30]1[CH2:34]O[CH2:32][CH2:31]1>CSC>[O:3]1[CH2:4][CH2:5][O:1][CH:2]1[C:6]1[CH:11]=[C:10]([O:12][CH3:13])[CH:9]=[CH:8][C:7]=1[C@H:14]([C:30]1[CH:34]=[CH:9][C:8]2[C:32](=[CH:10][CH:11]=[CH:6][CH:7]=2)[CH:31]=1)[CH2:15][C:16]([N:18]1[C@H:22]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH2:21][O:20][C:19]1=[O:29])=[O:17]

Participants

4

Reactant 2

HCID 8028Tetrahydrofuran2×HCID 66911576HCID 66911576, compound

Product 1

HCID 67056229HCID 67056229, compoundYield 85%

Reagents, catalysts & solvents 1

HCID 1068Dimethyl SulfideSolvent

Conditions

Temperature
-40 °C

Procedure

To a solution of copper(I) bromide-dimethyl sulfide complex (1.43 g, 6.9 mmol) in anhydrous THF (33 mL) and dimethyl sulfide (16.5 mL) at −78° C. was added 2-naphthylene magnesium bromide (27.3 mL, 0.5 M in THF) slowly via syringe. After the addition, the reaction solution was stirred at −40° C. for 30 min, and then re-cooled to −78° C. A solution of Compound 21 (1.8 g, 4.6 mmol) in THF (24 mL) was then added via syringe. The reaction mixture was slowly warmed to room temperature before it was quenched with aqueous ammonium chloride at 0° C. and extracted with ethyl acetate (2×). The combined organic extract was washed with 1:1 water/brine, dried over sodium sulfate and concentrated in vacuo. The residue obtained was purified by flash column chromatography (hexanes/ethyl acetate 95:5 to 55:45) to give Compound 22 (2.15 g, 85%) as an off-white foam: 1H NMR (CDCl3, 500 MHz) δ 7.72-7.70 (m, 2H), 7.69-7.63 (m, 2H), 7.46-7.40 (m, 2H), 7.37 (d, J=8.5 Hz, 1H), 7.24 (d, J=8.5 Hz, 1H), 7.17-7.11 (m, 2H), 7.04 (t, J=7.5 Hz, 2H), 6.99 (d, J=7.5 Hz, 2H), 6.81 (s, J=8.5 Hz, 1H), 6.09 (s, 1H), 5.34-5.30 (m, 2H), 4.59 (t, J=8.5 Hz, 1H), 4.16-4.14 (m, 3H), 4.06-4.01 (m, 3H), 3.79 (s, 3H), 3.60 (dd, J=16.5, 8.5 Hz, 1H).

Workup

  1. additionAfter the addition
  2. temperaturere-cooled to −78° C
  3. temperatureThe reaction mixture was slowly warmed to room temperature before it
  4. customwas quenched with aqueous ammonium chloride at 0° C.
  5. extractionextracted with ethyl acetate (2×)
  6. extractionThe combined organic extract
  7. washwas washed with 1:1 water/brine
  8. dry with materialdried over sodium sulfate
  9. concentrationconcentrated in vacuo
  10. customThe residue obtained
  11. customwas purified by flash column chromatography (hexanes/ethyl acetate 95:5 to 55:45)

Sources & evidence

ORD record
ord-264e0679d37c4f2e8bea23422e21f6c8
Source dataset
uspto-grants-2013_04
Patent number
US08420811B2

Reaction notes

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