Water → Tert-butyl 4-(3-(5-chloro-2-methyl-4-nitrophenoxy)propyl)piperazine-1-carboxylate

HRID 415065

Reaction equation

HRID 415065 reaction equation
[OH:1][CH2:2][CH2:3][CH2:4][N:5]1[CH2:10][CH2:9][N:8]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:7][CH2:6]1.[H-].[Na+].[Cl:20][C:21]1[CH:26]=[C:25](F)[C:24]([CH3:28])=[CH:23][C:22]=1[N+:29]([O-:31])=[O:30].O>C1COCC1>[Cl:20][C:21]1[C:22]([N+:29]([O-:31])=[O:30])=[CH:23][C:24]([CH3:28])=[C:25]([CH:26]=1)[O:1][CH2:2][CH2:3][CH2:4][N:5]1[CH2:10][CH2:9][N:8]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:7][CH2:6]1

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydride2×HCID 875934-Chloro-2-fluoro-5-nitrotolueneHCID 162178001-Boc-4-(3-hydroxypropyl)piperazine

Product 1

HCID 59349539Tert-butyl 4-(3-(5-chloro-2-methyl-4-nitrophenoxy)propyl)piperazine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
65 °C

Procedure

A flask was charged with tert-butyl 4-(3-hydroxypropyl)piperazine-1-carboxylate (905 mg, 3.7 mmol, commercially available from Alrich), sodium hydride, 95% (24 mg, 4.6 mmol) and THF (10 mL), and the mixture was stirred under N2 for 15 minutes, after which time a solution of 1-chloro-5-fluoro-4-methyl-2-nitrobenzene (700 mg, 3.7 mmol, commercially available from Aldrich) in THF (10 mL) was added to the sodium hydride mixture at 0° C. The reaction mixture was heated to 65° C. for 15 hours. Water was added to the cooled reaction mixture and the mixture was extracted with ethyl acetate. The organic solvent was concentrated under reduced pressure and the resulting solid was purified by silica column chromatography eluting with 5% methanol in dichloromethane, to give 1.2 g (78 5 yield) of tert-butyl 4-(3-(5-chloro-2-methyl-4-nitrophenoxy) propyl)piperazine-1-carboxylate. 1H-NMR (400 MHz, CDCl3) δ 7.82 (s, 1H), 6.92 (s, 1H), 3.92 (t, 2H), 3.06 (m, 4H), 2.62 (m, 4H), 2.36 (m, 2H), 2.34 (s, 3H), 1.84 (m, 2H), 1.42 (s, 9H). MS (EI): 414 (MH+).

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. concentrationThe organic solvent was concentrated under reduced pressure
  3. customthe resulting solid was purified by silica column chromatography
  4. washeluting with 5% methanol in dichloromethane

Sources & evidence

ORD record
ord-f13a68e64914483aa4daceb4a842ffb4
Source dataset
uspto-grants-2012_01
Patent number
US08088767B2

Linked notes

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