Ammonium Chloride → HCID 18434422, compound

HRID 1532780Notes

Reaction equation

HRID 1532780 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 (2x) 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, 1 H), 7.27 (m, 1 H), 7.07 (m, 5 H), 6.68 (m, 4 H), 4.40 (t, J=5.8 Hz, 2 H), 3.80 (s, 3 H), 2.88 (m, 6 H), 2.71 (m, 4 H), 1.81 (m, 4 H).

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 4 h
  3. washThe aqueous layer was washed with CHCl3 (2x)
  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-5d859132565a4964a1908b67034d456a
Source dataset
uspto-grants-2001_03
Patent number
US06204286B1

Reaction notes

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