4-Aminobenzonitrile → HCID 178462384, compound

HRID 480940Notes

Reaction equation

HRID 480940 reaction equation
C[Al](C)C.[NH2:5][C:6]1[CH:13]=[CH:12][C:9]([C:10]#[N:11])=[CH:8][CH:7]=1.[F:14][C:15]1[CH:20]=[C:19]([F:21])[CH:18]=[CH:17][C:16]=1[C@@:22]([OH:52])([CH2:46][N:47]1[CH:51]=[N:50][CH:49]=[N:48]1)[C@H:23]([S:25][C@@H:26]1[CH2:31][O:30][C@@H:29]([C:32]2[CH:33]=[C:34]3[C:39](=[CH:40][CH:41]=2)[CH:38]=[C:37]([C:42](OC)=[O:43])[CH:36]=[CH:35]3)[O:28][CH2:27]1)[CH3:24].C(C(C(C([O-])=O)O)O)([O-])=O.[Na+].[K+]>C1(C)C=CC=CC=1.O>[C:10]([C:9]1[CH:12]=[CH:13][C:6]([NH:5][C:42]([C:37]2[CH:36]=[CH:35][C:34]3[C:39](=[CH:40][CH:41]=[C:32]([C@H:29]4[O:28][CH2:27][C@H:26]([S:25][C@H:23]([CH3:24])[C@:22]([C:16]5[CH:17]=[CH:18][C:19]([F:21])=[CH:20][C:15]=5[F:14])([OH:52])[CH2:46][N:47]5[CH:51]=[N:50][CH:49]=[N:48]5)[CH2:31][O:30]4)[CH:33]=3)[CH:38]=2)=[O:43])=[CH:7][CH:8]=1)#[N:11]

Participants

7

Reactant 4

HCID 133964-AminobenzonitrileHCID 9855836Potassium sodium tartarateHCID 16682925TrimethylaluminumHCID 178497267HCID 178497267, compound

Product 1

HCID 178462384HCID 178462384, compoundYield 85.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1140TolueneSolvent2×

Procedure

Trimethylaluminium (0.67 ml, 1.07M n-hexane solution, 0.72 mmol) was added dropwise to a solution of commercially available 4-aminobenzonitrile (85 mg, 0.72 mmol) in anhydrous toluene (4 ml) at room temperature with stirring under a nitrogen atmosphere. After stirring the mixture at room temperature for 10 minutes, a solution of methyl 6-[trans-5-[[(1R,2R)-2-(2,4-difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]thio]-1,3-dioxan-2-yl]-2-naphthalenecarboxylate (100 mg, 0.18 mmol) in anhydrous toluene (3 ml) was added dropwise to the resulting mixture. This mixture was stirred at 80C for 2.5 hours. At the end of this time to the reaction mixture were added sequentially water and 0.5N aqueous potassium sodium (+)-tartrate solution at room temperature. The mixture was partitioned between ethyl acetate and water. The organic layer was washed with saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The resulting residue was chromatographed on a silica gel column using ethyl acetate-hexane (3:1) as the eluant to afford the title compound (99 mg, yield 85%) as a colorless oil which was recrystallized from ethyl acetate-hexane to give white powdery crystals.

Workup

  1. stirringAfter stirring the mixture at room temperature for 10 minutes
  2. customThe mixture was partitioned between ethyl acetate and water
  3. washThe organic layer was washed with saturated aqueous sodium chloride solution
  4. dry with materialdried over anhydrous magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe resulting residue was chromatographed on a silica gel column

Sources & evidence

ORD record
ord-917fc0eebe264f7ea6348f45b8ec1589
Source dataset
uspto-grants-2003_11
Patent number
US06653330B2

Reaction notes

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