HCID 67355477, compound → HCID 67353250, compound

HRID 1846157Notes

Reaction equation

HRID 1846157 reaction equation
[CH2:1]([O:8][C:9]1[C:10]([CH3:23])=[N:11][C:12]([N:16]2[C:20]([CH3:21])=[CH:19][CH:18]=[C:17]2[CH3:22])=[CH:13][C:14]=1[CH3:15])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Br[CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][O:34][CH2:35][O:36][CH3:37].[Li]C1C=CC=CC=1>C1COCC1.CCCCCC>[CH2:1]([O:8][C:9]1[C:10]([CH2:23][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][O:34][CH2:35][O:36][CH3:37])=[N:11][C:12]([N:16]2[C:17]([CH3:22])=[CH:18][CH:19]=[C:20]2[CH3:21])=[CH:13][C:14]=1[CH3:15])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 67355477HCID 67355477, compoundHCID 85780880HCID 85780880, compoundHCID 178506676HCID 178506676, compound

Product 1

HCID 67353250HCID 67353250, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent

Conditions

Temperature
-78 °C

Procedure

To a stirred solution at −78° C. containing 906 mg (2.95 mmol) of 3-(benzyloxy)-6-(2,5-dimethyl-1H-pyrrol-1-yl)-2,4-dimethylpyridine in 20 mL of anh. THF were added 789 mg (2.95 mmol) of 1-bromo-9-(methoxymethoxy)nonane followed by 1.99 mL (3.54 mmol) of a 1.80 M solution of PhLi in hexane. The reaction mixture was stirred at −78° C. for 30 min. then the reaction mixture was warmed to 23° C. slowly, and the reaction mixture was stirred 30 min. The reaction was quenched with satd aq ammonium chloride and then poured into 80 mL of water. The mixture was then extracted with two 80-mL portions of ethyl acetate. The combined organic layer was then washed with a 100-mL portion of brine, dried (MgSO4) and then concentrated under diminished pressure. The residue was purified by chromatography on a silica gel column (15×5 cm). Elution with 4:1 hexanes-ethyl acetate afforded the expected product as a light yellow oil: yield 877 mg (60%); silica gel TLC Rf 0.3 (9:1 hexanes-ethyl acetate); 1H NMR (CDCl3) δ 1.18-1.22 (br m, 12H), 1.50 (quint, 2H, J=6.8 Hz), 1.65 (m, 2H), 2.06 (s, 6H), 2.26 (s, 3H), 2.75 (dd, 2H, J=7.6, 7.6 Hz), 3.28 (s, 3H), 3.43 (t, 2H, J=6.8 Hz), 4.53 (s, 2H), 4.82 (s, 2H), 5.78 (s, 2H), 6.79, (s, 1H) and 7.29-7.40 (m, 5H); 13C NMR (CDCl3) δ 13.30, 13.30, 16.35, 26.19, 28.92, 29.40, 29.48, 29.50, 29.55, 29.61, 29.73, 32.13, 55.05, 67.86, 75.24, 96.36, 106.40, 106.40, 121.68, 121.68, 127.73, 127.90, 127.90, 128.89, 128.89, 138.83, 141.97, 141.97, 146.80, 150.76 and 155.88; mass spectrum (APCI), m/z 493.3426 (M+H)+ (C31H45N2O3 requires 493.3430).

Workup

  1. temperaturethe reaction mixture was warmed to 23° C. slowly
  2. stirringthe reaction mixture was stirred 30 min
  3. customThe reaction was quenched with satd aq ammonium chloride
  4. additionpoured into 80 mL of water
  5. extractionThe mixture was then extracted with two 80-mL portions of ethyl acetate
  6. washThe combined organic layer was then washed with a 100-mL portion of brine
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated under diminished pressure
  9. customThe residue was purified by chromatography on a silica gel column (15×5 cm)
  10. washElution with 4:1 hexanes-ethyl acetate

Sources & evidence

ORD record
ord-4a3212173f864558abcf913c366def25
Source dataset
uspto-grants-2015_02
Patent number
US08952025B2

Reaction notes

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