3,4-Dichloroaniline → HCID 22329434, compound

HRID 586416Notes

Reaction equation

HRID 586416 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][C:8]=1[Cl:9])[NH2:5].[H-].[Na+].[CH2:12]([N:19]1[CH2:24][CH2:23][N:22]([C:25]2[N:30]=[C:29]([N:31]3[CH2:40][CH2:39][C:34]4([O:38][CH2:37][CH2:36][O:35]4)[CH2:33][CH2:32]3)[CH:28]=[C:27](Cl)[N:26]=2)[CH2:21][CH2:20]1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1>O1CCCC1>[CH2:12]([N:19]1[CH2:20][CH2:21][N:22]([C:25]2[N:26]=[C:27]([NH:5][C:4]3[CH:6]=[CH:7][C:8]([Cl:9])=[C:2]([Cl:1])[CH:3]=3)[CH:28]=[C:29]([N:31]3[CH2:32][CH2:33][C:34]4([O:35][CH2:36][CH2:37][O:38]4)[CH2:39][CH2:40]3)[N:30]=2)[CH2:23][CH2:24]1)[C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1

Participants

5

Reactant 3

HCID 72573,4-DichloroanilineHCID 24758Sodium hydrideHCID 22329453HCID 22329453, compound

Product 1

HCID 22329434HCID 22329434, compoundYield 44%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A mixture of 3,4-dichloroaniline (1.7 g, 10.5 mmol) and NaH (0.50 g, 20.9 mmol) in tetrahydrofuran (20 mL) was heated at reflux for 30 minutes and then cooled to room temperature. A solution of 8-[2-(4-benzyl-1-piperazinyl)-6-chloro-4-pyrimidinyl]-1,4-dioxa-8-azaspiro[4.5]decane (3.0 g, 7.0 mmol) in tetrahydrofuran (30 mL) was added to this mixture and the resulting solution was stirred for 22.5 hours. The reaction mixture was quenched with saturated NH4Cl, concentrated under reduced pressure, and redissolved in EtOAc. The organic layer was separated and washed with aqueous citric acid (2×300 mL), water (2×300 mL), and brine (2×300 mL). The crude product was purified by column chromatography [eluent: EtOAc/hexane (1:4)], giving the desired product (1.7 g, 44%).

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 30 minutes
  3. customThe reaction mixture was quenched with saturated NH4Cl
  4. concentrationconcentrated under reduced pressure
  5. dissolutionredissolved in EtOAc
  6. customThe organic layer was separated
  7. washwashed with aqueous citric acid (2×300 mL), water (2×300 mL), and brine (2×300 mL)
  8. customThe crude product was purified by column chromatography [eluent: EtOAc/hexane (1:4)]

Sources & evidence

ORD record
ord-97cb1376da71413194c5011e6b5644f0
Source dataset
uspto-grants-2005_08
Patent number
US06936607B2

Reaction notes

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