Tert-Butyl nitrite → Ethyl 5-chloro-1-(pyridin-2-YL)-1H-pyrazole-4-carboxylate

HRID 1941878Notes

Reaction equation

HRID 1941878 reaction equation
N[C:2]1[N:6]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][N:8]=2)[N:5]=[CH:4][C:3]=1[C:13]([O:15][CH2:16][CH3:17])=[O:14].[Cl:18]N1C(=O)CCC1=O.N(OC(C)(C)C)=O>ClCCl>[Cl:18][C:2]1[N:6]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][N:8]=2)[N:5]=[CH:4][C:3]=1[C:13]([O:15][CH2:16][CH3:17])=[O:14]

Participants

5

Reactant 3

HCID 10906Tert-Butyl nitriteHCID 31398ChlorosuccinimideHCID 742041ethyl 5-amino-1-(pyridin-2-yl)-1H-pyrazole-4-carboxylate

Product 1

HCID 13654084Ethyl 5-chloro-1-(pyridin-2-YL)-1H-pyrazole-4-carboxylate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of ethyl 5-amino-1-(pyridin-2-yl)-1H-pyrazole-4-carboxylate (200 mg, 0.861 mmol) and 1-chloropyrrolidine-2,5-dione (172 mg, 1.292 mmol) in dichloromethane (8 mL) was added tert-butyl nitrite (0.154 mL, 1.292 mmol). The reaction mixture was stirred at rt for 30 minutes, after which time it was concentrated to yield a crude product which was purified on a silica gel column eluting with hexanes/EtOAc to yield ethyl 5-chloro-1-(pyridin-2-yl)-1H-pyrazole-4-carboxylate. The material from Method 1 and Method 2 were combined (106 mg, 0.42 mmol). HPLC ret. time=2.50 min. HPLC: Column: YMC S5 COMBISCREEN® 4.6×50 mm; Gradient time: 4 min; Flow rate=4 mL/min; Solvent A=10% MeOH—90% Water—0.2% H3PO4; Solvent B=90% MeOH—10% water—0.2% H3PO4; Start % B=0; Final % B=100. LC-MS: M+1=252.1. 1H NMR (400 MHz, MeOD) δ ppm 8.61 (1 H, dd, J=4.89, 1.13 Hz), 8.16 (1 H, s), 8.09 (1 H, td, J=7.78, 1.76 Hz), 7.74 (1 H, d, J=8.03 Hz), 7.57 (1 H, ddd, J=7.53, 4.77, 1.00 Hz), 4.36 (2 H, q, J=7.28 Hz), 1.38 (3 H, t, J=7.15 Hz).

Workup

  1. concentrationafter which time it was concentrated
  2. customto yield a crude product which
  3. customwas purified on a silica gel column
  4. washeluting with hexanes/EtOAc

Sources & evidence

ORD record
ord-ec949f637d714b6a92679ef3bcbd3e35
Source dataset
uspto-grants-2013_03
Patent number
US08389509B2

Reaction notes

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