Diethyl Ether → 4-[4-(6-Fluoro-1H-indazol-3-yl)-1-piperazinyl]2-hydroxy-2-methylbutane Hydrochloride

HRID 742738Notes

Reaction equation

HRID 742738 reaction equation
[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([N:11]3[CH2:16][CH2:15][N:14]([CH2:17][CH2:18]C(OCC)=O)[CH2:13][CH2:12]3)=[N:7][NH:8]2)=[CH:4][CH:3]=1.[CH3:24][Mg]Br.[NH4+].[Cl-:28].CC[O:31][CH2:32][CH3:33]>C1COCC1>[ClH:28].[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([N:11]3[CH2:12][CH2:13][N:14]([CH2:17][CH2:18][C:32]([OH:31])([CH3:33])[CH3:24])[CH2:15][CH2:16]3)=[N:7][NH:8]2)=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 3283Diethyl EtherHCID 25517Ammonium ChlorideHCID 18467273HCID 18467273, compoundHCID 178418573HCID 178418573, compound

Product 1

HCID 184673304-[4-(6-Fluoro-1H-indazol-3-yl)-1-piperazinyl]2-hydroxy-2-methylbutane Hydrochloride

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of ethyl 3-[4-(6-fluoro-1H-indazol-3-yl)-1-piperazinyl]propionate (5.0 g, 16 mmol) in THF (120 ml) under N2 was added, dropwise, methylmagnesium bromide (15.6 ml of a 3.0M solution in Et2O; 0.047 mol). The temperature was maintained below 30° C. during the addition by using a water bath. After complete addition, the reaction was stirred at ambient temperature for 5 hours The reaction was cooled in an ice bath and saturated NH4Cl (25 ml) was added. The mixture was extracted with EtOAc, and the EtOAc extract was washed with H2O, dried with Na2SO4 and concentrated to yield 5.0 g of a white solid. The product was recrystallized from EtOAc to yield 3.8 g of white crystalline flakes. The compound was dissolved in anhydrous Et2O (200 ml) and MeOH (20 ml) and the insolubles were filtered away. The filtrate was acidified with ethereal HCl to precipitate the salt. Additional anhydrous Et2O (200 ml) was added and the suspension was stirred 15 minutes. The solid was collected to yield 4.5 g of a white powder. Two recrystallizations from MeOH gave 2.2 g. The concentrated mother liquor from the MeOH recrystallizations (2.0 g) was recrystallized from DMF to afford 1.2 g. The two samples were combined and a final recrystallization from MeOH provided 3.0 g (57%) of a white powder m.p.=254°-256° C.

Workup

  1. temperatureThe temperature was maintained below 30° C. during the addition
  2. additionAfter complete addition
  3. temperaturewas cooled in an ice bath
  4. extractionThe mixture was extracted with EtOAc
  5. extractionthe EtOAc extract
  6. washwas washed with H2O
  7. dry with materialdried with Na2SO4
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-8748b86abe1f4c6e8b10483a12b33e10
Source dataset
uspto-grants-1996_09
Patent number
US05554614

Reaction notes

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