2-(4-Fluorophenyl)acetyl isocyanate → HCID 23152968, compound

HRID 492928Notes

Reaction equation

HRID 492928 reaction equation
[NH2:1][C:2]1[CH:30]=[CH:29][C:5]([O:6][C:7]2[CH:12]=[CH:11][N:10]=[C:9]([NH:13][C:14]([N:16]3[CH2:21][CH2:20][N:19]([CH:22]4[CH2:27][CH2:26][N:25]([CH3:28])[CH2:24][CH2:23]4)[CH2:18][CH2:17]3)=[O:15])[CH:8]=2)=[CH:4][CH:3]=1.[F:31][C:32]1[CH:37]=[CH:36][C:35]([CH2:38][C:39]([N:41]=[C:42]=[O:43])=[O:40])=[CH:34][CH:33]=1>O1CCCC1.C(OCC)(=O)C.CCCCCC>[F:31][C:32]1[CH:33]=[CH:34][C:35]([CH2:38][C:39]([NH:41][C:42](=[O:43])[NH:1][C:2]2[CH:3]=[CH:4][C:5]([O:6][C:7]3[CH:12]=[CH:11][N:10]=[C:9]([NH:13][C:14]([N:16]4[CH2:17][CH2:18][N:19]([CH:22]5[CH2:23][CH2:24][N:25]([CH3:28])[CH2:26][CH2:27]5)[CH2:20][CH2:21]4)=[O:15])[CH:8]=3)=[CH:29][CH:30]=2)=[O:40])=[CH:36][CH:37]=1

Participants

6

Reactant 2

HCID 231530882-(4-Fluorophenyl)acetyl isocyanateHCID 23153199HCID 23153199, compound

Product 1

HCID 23152968HCID 23152968, compoundYield 49%

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolventHCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

To a solution of 4-(4-aminophenoxy)-2-{[4-(1-methylpiperidin-4-yl)piperazin-1-yl]carbonylamino}pyridine (834 mg) in tetrahydrofuran (45 ml) was added a solution of 2-(4-fluorophenyl)acetyl isocyanate in ethyl acetate (0.25 M, 15 ml) at room temperature, followed by stirring for 3.5 hours. The reaction mixture was partitioned between ethyl acetate and a saturated aqueous solution of sodium hydrogencarbonate. The organic layer was washed with brine and dried over anhydrous sodium sulfate. The solvent was evaporated to give a residue, which was then purified by silica gel column chromatography (Fuji Silysia NH, eluent; ethyl acetate, then ethyl acetate:methanol=97:3). Fractions containing the target compound were concentrated to give a residue, which was then suspended in ethyl acetate (8 ml) and hexane (16 ml). The crystals were filtered off and dried under aeration to provide the titled compound (546 mg, 49%) as white crystals.

Workup

  1. customThe reaction mixture was partitioned between ethyl acetate
  2. washThe organic layer was washed with brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. customThe solvent was evaporated
  5. customto give a residue, which
  6. customwas then purified by silica gel column chromatography (Fuji Silysia NH, eluent
  7. additionFractions containing the target compound
  8. concentrationwere concentrated
  9. customto give a residue, which
  10. filtrationThe crystals were filtered off
  11. customdried under aeration

Sources & evidence

ORD record
ord-ff28250607c24ac99469dc3dd922f9a4
Source dataset
uspto-grants-2009_05
Patent number
US07531532B2

Reaction notes

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