tert-Butanol → N-benzyloxycarbonyl-5-aminomethyl-4-(4-pyridyl)-3-(4-fluorophenyl)pyrazole

HRID 2230386Notes

Reaction equation

HRID 2230386 reaction equation
[CH3:1][C:2]([O-])([CH3:4])[CH3:3].[K+].[CH3:7][C:8](O)([CH3:10])C.[F:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]2[NH:23][N:22]=[C:21](N3CCN(C(OC(C)(C)C)=O)CC3)[C:20]=2[C:37]2[CH:42]=[CH:41][N:40]=[CH:39][CH:38]=2)=[CH:15][CH:14]=1.C(O[C:51]([NH:53]CC(C1CC(=O)N(O)C1=O)=O)=O)C1C=CC=CC=1.[OH2:65].NN.C1[CH2:72][O:71]CC1>O.C(OCC)(=O)C.CC(O)=O>[CH2:1]([O:65][C:72]([N:22]1[C:21]([CH2:51][NH2:53])=[C:20]([C:37]2[CH:38]=[CH:39][N:40]=[CH:41][CH:42]=2)[C:19]([C:16]2[CH:15]=[CH:14][C:13]([F:12])=[CH:18][CH:17]=2)=[N:23]1)=[O:71])[C:2]1[CH:4]=[CH:10][CH:8]=[CH:7][CH:3]=1

Participants

10

Reactant 6

HCID 6386tert-ButanolHCID 8028Tetrahydrofuran3×HCID 24654Hydrazine hydrate (1:1)HCID 22037183N-benzyloxycarbonyl-glycyl-N-hydroxysuccinimideHCID 220373211,1-dimethylethyl 4-[5-(4-fluorophenyl)-4-(4-pyridinyl)-1H-pyrazol-3-yl]-1-piperazinecarboxylateHCID 23665647Potassium tert-butoxide

Product 1

HCID 69409299N-benzyloxycarbonyl-5-aminomethyl-4-(4-pyridyl)-3-(4-fluorophenyl)pyrazole

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

A 3 L round bottom flask fitted with a mechanical stirrer, N2 inlet and an addition funnel was was charged wtih 557 mL (0.56 mol) of 1 M t-BuOK in THF and 53 mL (0.56 mol) of t-BuOH. The ketone, 1 (60 g, 0.28 mol) was dissolved in 600 mL of THF and added to the stirred mixture at room temperature. A yellow precipitate formed and the mixture was stirred for 1 h. N-benzyloxycarbonyl-glycinyl N-hydroxysuccinimide (128.6 g, 0.42 mol) was dissolved in 600 mL of THF and added dropwise at r.t. over 1 h. The mixture was stirred for another 5 minutes and 150 mL of water was added. the pH was adjusted to 6.7 with 70 mL of AcOH. Hydrazine monohydrate (41 mL in 100 mL of water) was added via an addition funnel. The mixture was stirred for 1 h and was diluted with 500 mL of water and 500 mL of ethyl acetate. The biphasic mixture was transferred to a sep funnel and the layers were separated. The aqueous layer was extracted with EtOAc (3×300 mL). The organic layer was dried (Na2SO4), filtered and evaporated to leave 157 g of a crude reddish oil.

Workup

  1. customA 3 L round bottom flask fitted with a mechanical stirrer, N2 inlet and an addition funnel
  2. additionadded to the stirred mixture at room temperature
  3. customA yellow precipitate formed
  4. additionadded dropwise at r.t. over 1 h
  5. stirringThe mixture was stirred for another 5 minutes
  6. stirringThe mixture was stirred for 1 h
  7. customThe biphasic mixture was transferred to a sep funnel
  8. customthe layers were separated
  9. extractionThe aqueous layer was extracted with EtOAc (3×300 mL)
  10. dry with materialThe organic layer was dried (Na2SO4)
  11. filtrationfiltered
  12. customevaporated

Sources & evidence

ORD record
ord-a7c6c0e1c8ac4a8fbdb88d38d270d7c2
Source dataset
uspto-grants-2002_07
Patent number
US06423713B1

Reaction notes

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