Epichlorohydrin → 3-(4-Chloro-3-methyl-phenyl)-1-oxiranylmethyl-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-5-carboxylic acid tert-butyl ester

HRID 970112Notes

Reaction equation

HRID 970112 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]2[NH:14][N:15]=[C:16]([C:17]3[CH:22]=[CH:21][C:20]([Cl:23])=[C:19]([CH3:24])[CH:18]=3)[C:10]=2[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:25]([CH:27]1[O:29][CH2:28]1)Cl.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C.CCOC(C)=O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]2[N:14]([CH2:25][CH:27]3[CH2:28][O:29]3)[N:15]=[C:16]([C:17]3[CH:22]=[CH:21][C:20]([Cl:23])=[C:19]([CH3:24])[CH:18]=3)[C:10]=2[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 7835EpichlorohydrinHCID 10796Cesium carbonateHCID 684601723-(4-Chloro-3-methyl-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-5-carboxylic acid tert-butyl ester

Product 1

HCID 865848173-(4-Chloro-3-methyl-phenyl)-1-oxiranylmethyl-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-5-carboxylic acid tert-butyl esterYield 57%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 3-(4-chloro-3-methyl-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-5-carboxylic acid tert-butyl ester (18.26 g, 53 mmol) and epichlorohydrin (41.12 mL, 526 mmol) in DMF (100 mL) was added cesium carbonate (20.56 g, 63 mmol). The reaction mixture was allowed to stir for 72 h, diluted with EtOAc (200 mL) and washed with saturated NaHCO3 and brine. The organic layer was dried over Na2SO4, concentrated and purified by column chromatography (silica, 20% acetone/CH2Cl2) to afford 3-(4-chloro-3-methyl-phenyl)-1-oxiranylmethyl-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-5-carboxylic acid tert-butyl ester (12.0 g, 57%). TLC (silica, 20% acetone/CH2Cl2): Rf=0.68. MS (electrospray) m/z 491.2 (491.2, calculated for C27H31ClN6O, [M+H]+). 1H NMR (400 MHz, CDCl3) 7.55 (s, 1H), 7.36 (m, 2H), 4.61 (m, 2H), 4.38-4.47 (m, 1H), 4.11 (dd, J=14.3, 5.7 Hz, 1H), 3.67-3.79 (m, 2H), 3.34 (m, 1H), 2.83 (t, J=4.5 Hz, 1H), 2.75 (m, 2H), 2.51 (m, 1H), 2.41 (s, 3H), 1.48 (s, 9H).

Workup

  1. washwashed with saturated NaHCO3 and brine
  2. dry with materialThe organic layer was dried over Na2SO4
  3. concentrationconcentrated
  4. custompurified by column chromatography (silica, 20% acetone/CH2Cl2)

Sources & evidence

ORD record
ord-cb4d4628acff4725a7685af759020707
Source dataset
uspto-grants-2007_12
Patent number
US07309703B2

Reaction notes

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