Diisopropylethylamine → HCID 118383363, compound

HRID 2202728Notes

Reaction equation

HRID 2202728 reaction equation
Cl.[NH:2]([C@H:4]1[CH2:9][CH2:8][C@H:7]([C:10]([O:12][CH2:13][CH3:14])=[O:11])[C@H:6]([CH3:15])[CH2:5]1)[NH2:3].CCN(C(C)C)C(C)C.CN(/[CH:28]=[C:29](/[C:40](=O)[C:41]([F:44])([F:43])[F:42])\[C:30]([O:32][CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)=[O:31])C.CCOC(C)=O.CCCCCC>CCO>[CH2:13]([O:12][C:10]([C@H:7]1[CH2:8][CH2:9][C@H:4]([N:2]2[C:40]([C:41]([F:44])([F:42])[F:43])=[C:29]([C:30]([O:32][CH2:33][C:34]3[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=3)=[O:31])[CH:28]=[N:3]2)[CH2:5][C@H:6]1[CH3:15])=[O:11])[CH3:14]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 21226206Ethyl acetate hexaneHCID 118343023HCID 118343023, compoundHCID 131735771HCID 131735771, compound

Product 1

HCID 118383363HCID 118383363, compoundYield 76%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Procedure

To a 250-mL round-bottomed flask was added (1S,2R,4S)-ethyl 4-hydrazinyl-2-methylcyclohexanecarboxylate hydrochloride (4.00 g, 16.90 mmol) and DIPEA (4.43 ml, 25.3 mmol) in EtOH (84 ml). Then a solution of (Z)-benzyl 2-((dimethylamino)methylene)-4,4,4-trifluoro-3-oxobutanoate (5.09 g, 16.90 mmol) in EtOH (84 ml) was added dropwise into the reaction mixture. The overall reaction mixture was allowed to stir under inert atmosphere, while at ambient temperature overnight. The progress of the reaction was monitored by LC/MS and TLC (30% EtOAc/hexane) which showed mostly desired material LCMS (ESI) m/z 461.2 (M+Na)+, without any starting material remaining. The reaction mixture was concentrated in-vacuo. The crude material was purified by chromatography through an Interchim (25 micron) silica-gel column (200 g), eluting with a gradient of 0-30% EtOAc in hexane, to provide benzyl 1-((1S,3R,4S)-4-(ethoxycarbonyl)-3-methylcyclohexyl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate (5.631 g, 12.84 mmol, 76% yield) as light-yellow oil. 1H NMR (400 MHz, DMSO-d6) δ 8.14 (s, 1H), 7.32-7.45 (m, 5H), 5.30 (s, 2H), 4.55-4.65 (m, 1H), 4.02-4.15 (m, 2H), 2.65 (td, J=4.50, 11.54 Hz, 1H), 2.13 (dt, J=4.50, 12.42 Hz, 1H), 1.95-2.04 (m, 2H), 1.73 (d, J=4.89 Hz, 3H), 1.16-1.23 (m, 3H), 0.92 (d, J=7.04 Hz, 3H); LCMS (ESI) m/z 461.2 (M+Na)+.

Workup

  1. concentrationThe reaction mixture was concentrated in-vacuo
  2. customThe crude material was purified by chromatography through an Interchim (25 micron) silica-gel column (200 g)
  3. washeluting with a gradient of 0-30% EtOAc in hexane

Sources & evidence

ORD record
ord-6b86e1ac45c04784a0d3f7c36c3185d4
Source dataset
uspto-grants-2016_06
Patent number
US09365522B2

Reaction notes

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