Lithium Hydroxide → HCID 58919231, compound

HRID 539711Notes

Reaction equation

HRID 539711 reaction equation
[F:1][C:2]1[C:21]([C:22](OC)=[O:23])=[C:20]([F:26])[CH:19]=[CH:18][C:3]=1[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.[Li+].[OH-].ON1C(=O)CCC1=O.C1CCC(N=C=NC2CCCCC2)CC1.[N-:52]=[N+:53]=[N-:54].[Na+]>C1COCC1.O>[N:52]([C:22]([C:21]1[C:2]([F:1])=[C:3]([CH:18]=[CH:19][C:20]=1[F:26])[CH2:4][N:5]1[CH2:10][CH2:9][N:8]([C:11]([O:13][C:14]([CH3:15])([CH3:17])[CH3:16])=[O:12])[CH2:7][CH2:6]1)=[O:23])=[N+:53]=[N-:54]

Participants

8

Reactant 5

HCID 3939Lithium HydroxideHCID 10868DicyclohexylcarbodiimideHCID 33557Sodium AzideHCID 80170N-HydroxysuccinimideHCID 58919227HCID 58919227, compound

Product 1

HCID 58919231HCID 58919231, compoundYield 122.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a room temperature solution of tert-butyl 4-(2,4-difluoro-3-(methoxycarbonyl)benzyl)piperazine-1-carboxylate (2.0 g, 5.4 mmol, 1.0 equiv) in THF (5.0 mL) was added a solution of LiOH (249 mg, 5.94 mmol, 1.1 equiv) in water (5 mL). The resulting mixture was stirred overnight. The resulting lithium carboxylate salt was concentrated in vacuo and used in the next step without purification. The lithium salt was suspended in dioxane (50 mL), and N-hydroxysuccinimide (652 mg, 5.67 mmol, 1.05 equiv) and DCC (1.28 g, 6.21 mmol, 1.15 equiv) were added as solids. After the reaction mixture was stirred for 2 days, it was charged with sodium azide (340 mg, 5.4 mmol, 1.0 equiv) and then stirred overnight. The resulting solid was filtered and washed with DCM. The organic layer was passed through a plug of silica gel and concentrated in vacuo to provide tert-butyl 4-(3-(azidocarbonyl)-2,4-difluorobenzyl)piperazine-1-carboxylate (2.52 g crude) which was taken on to the next step without purification.

Workup

  1. concentrationThe resulting lithium carboxylate salt was concentrated in vacuo
  2. customused in the next step without purification
  3. stirringAfter the reaction mixture was stirred for 2 days
  4. stirringstirred overnight
  5. filtrationThe resulting solid was filtered
  6. washwashed with DCM
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-5853091de41046539a040f4092060d81
Source dataset
uspto-grants-2014_10
Patent number
US08871768B2

Reaction notes

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