Ammonium Chloride → HCID 18434422, compound

HRID 1859086Notes

Reaction equation

HRID 1859086 reaction equation
[C:1]1([Li])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Br[C:9]1[CH2:18][CH2:17][C:16]2[C:11](=[CH:12][CH:13]=[C:14]([O:19][CH3:20])[CH:15]=2)[C:10]=1[C:21]1[CH:22]=[CH:23][C:24]([O:27][CH2:28][CH2:29][N:30]2[CH2:34][CH2:33][CH2:32][CH2:31]2)=[N:25][CH:26]=1.[NH4+].[Cl-]>C1COCC1.[Cl-].[Zn+2].[Cl-].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:20][O:19][C:14]1[CH:15]=[C:16]2[C:11](=[CH:12][CH:13]=1)[C:10]([C:21]1[CH:22]=[CH:23][C:24]([O:27][CH2:28][CH2:29][N:30]3[CH2:34][CH2:33][CH2:32][CH2:31]3)=[N:25][CH:26]=1)=[C:9]([C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1)[CH2:18][CH2:17]2

Participants

7

Reactant 3

HCID 25517Ammonium ChlorideHCID 18434416HCID 18434416, compoundHCID 178506676HCID 178506676, compound

Product 1

HCID 18434422HCID 18434422, compoundYield 69.3%

Reagents, catalysts & solvents 3

HCID 3007855ZincchlorideCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

Phenyllithium (1.8 M in cyclohexane/ether, 3.8 mL, 7.0 mmol) was added slowly to zinc chloride (0.5 M in THF, 14 mL, 7.0 mmol) at 0° C. After stirring for 15 min, 5-(2-bromo-6-methoxy-3,4-dihydronaphthalen-1-yl)-2-(2-pyrrolidin-1-ylethoxy)pyridine (1.0 g, 2.3 mmol) in dry THF (20 mL) was added followed by Pd(PPh3)4 (200 mg, 0.173 mmol). The reaction was warmed to room temperature and was heated at reflux for 4 h. The reaction was poured into aqueous NH4Cl solution (satd). The aqueous layer was washed with CHCl3 (2×) and the combined organic solutions were washed with water followed by brine. The organic solution was dried (MgSO4), filtered, and concentrated in vacuo. Flash chromatography (CHCl3 :MeOH, 95:5) provided the title compound (680 mg, 68%). 1H NMR (250 MHz, CDCl3): δ7.78 (d, J=2.1 Hz, 1H), 7.27 (m, 1H), 7.07 (m, 5H), 6.68 (m, 4H), 4.40 (t, J=5.8 Hz, 2H), 3.80 (s, 3H), 2.88 (m, 6H), 2.71 (m, 4 H), 1.81 (m, 4H).

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 4 h
  3. washThe aqueous layer was washed with CHCl3 (2×)
  4. washthe combined organic solutions were washed with water
  5. dry with materialThe organic solution was dried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-b0b1807884ee46c38476edbdc8344640
Source dataset
uspto-grants-2000_11
Patent number
US06153622

Reaction notes

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