Tetrahydrofuran → HCID 66926944, compound

HRID 81065Notes

Reaction equation

HRID 81065 reaction equation
[Cl:1][C:2]1[C:7]([C:8]#[N:9])=[C:6]([C:10]2[CH:15]=[CH:14][C:13]([O:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)=[CH:12][CH:11]=2)[N:5]=[C:4]([C:23]2[CH:28]=[CH:27][C:26]([N+:29]([O-])=O)=[CH:25][CH:24]=2)[CH:3]=1.[Cl-].[NH4+].C1COCC1>[Zn].CO>[NH2:29][C:26]1[CH:25]=[CH:24][C:23]([C:4]2[CH:3]=[C:2]([Cl:1])[C:7]([C:8]#[N:9])=[C:6]([C:10]3[CH:15]=[CH:14][C:13]([O:16][C:17]4[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=4)=[CH:12][CH:11]=3)[N:5]=2)=[CH:28][CH:27]=1

Participants

6

Reactant 3

HCID 8028TetrahydrofuranHCID 25517Ammonium ChlorideHCID 669270004-Chloro-6-(4-nitrophenyl)-2-(4-phenoxyphenyl)nicotinonitrile

Product 1

HCID 66926944HCID 66926944, compoundYield 40.2%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 887MethanolSolvent

Procedure

A mixture of 4-chloro-6-(4-nitrophenyl)-2-(4-phenoxyphenyl)nicotinonitrile (136.3 mg, 0.319 mmol), zinc dust (312 mg, 4.78 mmol), ammonium chloride (256 mg, 4.78 mmol), THF (3 mL) and methanol (3 mL) was stirred at room temperature for 15 min, and filtered. The filtrate was concentrated and partitioned with dichloromethane and saturated sodium bicarbonate. The organic layer was separated and concentrated. Silica gel chromatography, eluting with 0-40% ethyl acetate in hexanes, gave pure 6-(4-aminophenyl)-4-chloro-2-(4-phenoxyphenyl)nicotinonitrile as yellow solid (51 mg). 1H NMR (400 MHz, CDCl3) δ ppm 7.96-8.04 (4H, m), 7.70 (1H, s), 7.40 (2H, t, J=8.03 Hz), 7.18 (1H, t, J=7.40 Hz), 7.08-7.14 (4H, m), 6.76 (2H, δ, J=8.78 Hz), 4.04 (2H, s); MS (ES+) m/z: 398 (M+H); LC retention time: 4.551 min (analytical HPLC Method A). Additional impure product was also obtained from the chromatography (48.1 mg).

Workup

  1. filtrationfiltered
  2. concentrationThe filtrate was concentrated
  3. custompartitioned with dichloromethane and saturated sodium bicarbonate
  4. customThe organic layer was separated
  5. concentrationconcentrated
  6. washSilica gel chromatography, eluting with 0-40% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-509b039825f144e680a55a26c46d6e35
Source dataset
uspto-grants-2014_09
Patent number
US08846673B2

Reaction notes

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