Sodium hydride → HCID 86596679, compound

HRID 1373637Notes

Reaction equation

HRID 1373637 reaction equation
[F:1][C:2]1([F:15])[O:7][C:6]2[CH:8]=[CH:9][CH:10]=[C:11]([NH2:12])[C:5]=2[O:4][C:3]1([F:14])[F:13].[C:16]([O:20][C:21](=[O:29])[N:22]([CH2:26][CH2:27]Cl)[CH2:23][CH2:24]Cl)([CH3:19])([CH3:18])[CH3:17].[H-].[Na+]>CN(C=O)C>[C:16]([O:20][C:21]([N:22]1[CH2:26][CH2:27][N:12]([C:11]2[C:5]3[O:4][C:3]([F:13])([F:14])[C:2]([F:1])([F:15])[O:7][C:6]=3[CH:8]=[CH:9][CH:10]=2)[CH2:24][CH2:23]1)=[O:29])([CH3:19])([CH3:18])[CH3:17]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 27765722,2,3,3-Tetrafluoro-2,3-dihydro-1,4-benzodioxin-5-amineHCID 11230235N-BOC-N,N-Bis(2-chloroethyl)amine

Product 1

HCID 86596679HCID 86596679, compoundYield 33.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

An intermediate compound, 1-(2,2,3,3-Tetrafluoro-2,3-dihydro-benzo[1,4]dioxin-5-yl)-piperazine, was produced as follows: To the mixture of 2,2,3,3-tetrafluoro-2,3-dihydro-benzo[1,4]dioxin-5-ylamine (8.9 g, 40 mmol) and bis-(2-chloro-ethyl)-carbamic acid tert-butyl ester (14.5 g, 60 mmol) in DMF (200 mL) was added NaH (3.2 g, 60% oil dispersion, 80 mmol) at 0° C. and the resulting mixture was stirred at the same temperature for 1.0 h. No reaction was observed by TLC. The mixture was further stirred at room temperature for 4.0 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-(2,2,3,3-tetrafluoro-2,3-dihydro-benzo[1,4]dioxin-5-yl)-piperazine-1-carboxylic acid tert-butyl ester (5.2 g, 33%) as colorless crystals.

Workup

  1. stirringThe mixture was further stirred at room temperature for 4.0 h until LCMS
  2. customThe reaction was quenched with aq. NH4Cl
  3. extractionextracted with EtOAc
  4. washwashed with brine
  5. customdried
  6. concentrationconcentrated
  7. customThe residue was purified by flash chromatography (Et3N:EtOAc:heptane/1:10:100)

Sources & evidence

ORD record
ord-662ad829ee99421c9ebabcb1ce0032a9
Source dataset
uspto-grants-2007_01
Patent number
US07160888B2

Reaction notes

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