Sodium hydride → 4-(2,2-Difluoro-benzo[1,3]dioxol-4-yl)-piperazine-1-carboxylic acid tert-butyl ester

HRID 1373638Notes

Reaction equation

HRID 1373638 reaction equation
[F:1][C:2]1([F:12])[O:6][C:5]2[CH:7]=[CH:8][CH:9]=[C:10]([NH2:11])[C:4]=2[O:3]1.[C:13]([O:17][C:18](=[O:26])[N:19]([CH2:23][CH2:24]Cl)[CH2:20][CH2:21]Cl)([CH3:16])([CH3:15])[CH3:14].[H-].[Na+]>CN(C=O)C>[C:13]([O:17][C:18]([N:19]1[CH2:23][CH2:24][N:11]([C:10]2[C:4]3[O:3][C:2]([F:1])([F:12])[O:6][C:5]=3[CH:7]=[CH:8][CH:9]=2)[CH2:21][CH2:20]1)=[O:26])([CH3:16])([CH3:15])[CH3:14]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 27368912,2-Difluoro-1,3-dioxaindan-4-amineHCID 11230235N-BOC-N,N-Bis(2-chloroethyl)amine

Product 1

HCID 694174874-(2,2-Difluoro-benzo[1,3]dioxol-4-yl)-piperazine-1-carboxylic acid tert-butyl esterYield 22.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

An intermediate compound, 1-(2,2-Difluoro-benzo[1,3]dioxol-4-yl)-piperazine, was produced as follows: To the mixture of 2,2-difluoro-benzo[1,3]dioxol-4-ylamine (27 g, 0.156 mol) and bis-(2-chloro-ethyl)-carbamic acid tert-butyl ester (75.5 g, 0.31 mol) in DMF (500 mL) was added NaH (15.6 g, 60% oil dispersion, 0.39 mol) at 0° C. and the resulting mixture was stirred at room temperature for 24 h until LCMS indicated the starting material disappeared. The reaction was quenched with aq. NH4Cl, extracted with EtOAc, washed with brine, dried and concentrated. The residue was purified by flash chromatography (Et3N:EtOAc:heptane/1:10:100) to afford 4-(2,2-difluoro-benzo[1,3]dioxol-4-yl)-piperazine-1-carboxylic acid tert-butyl ester (12.0 g, 22%) as colorless crystals.

Workup

  1. customThe reaction was quenched with aq. NH4Cl
  2. extractionextracted with EtOAc
  3. washwashed with brine
  4. customdried
  5. concentrationconcentrated
  6. customThe residue was purified by flash chromatography (Et3N:EtOAc:heptane/1:10:100)

Sources & evidence

ORD record
ord-8e099b4593f5486a974eba2aa0e3f8f2
Source dataset
uspto-grants-2007_01
Patent number
US07160888B2

Reaction notes

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