Carbon Dioxide → tert-butyl {[(1S,2S)-2-(2-methylpyrazolo[1,5-a]pyridin-4-yl)cyclopropyl]methyl}carbamate

HRID 1639872Notes

Reaction equation

HRID 1639872 reaction equation
[C:1]([O:5][C:6](=[O:22])[NH:7][CH2:8][C@@H:9]1[CH2:11][C@H:10]1[C:12]1[C:13]2[N:14]([N:18]=[C:19]([CH3:21])[CH:20]=2)[CH:15]=[CH:16][CH:17]=1)([CH3:4])([CH3:3])[CH3:2].CC(NCCC#N)CC1C=CC=CC=1.Cl.C(=O)=O>CO>[C:1]([O:5][C:6](=[O:22])[NH:7][CH2:8][C@H:9]1[CH2:11][C@@H:10]1[C:12]1[C:13]2[N:14]([N:18]=[C:19]([CH3:21])[CH:20]=2)[CH:15]=[CH:16][CH:17]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 280Carbon DioxideHCID 161245Fenproporex hydrochlorideHCID 59334467tert-butyl {[(1R,2R)-2-(2-methylpyrazolo[1,5-a]pyridin-4-yl)cyclopropyl]methyl}carbamate

Product 1

HCID 59334527tert-butyl {[(1S,2S)-2-(2-methylpyrazolo[1,5-a]pyridin-4-yl)cyclopropyl]methyl}carbamateYield 46%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

Trans-tert-butyl{[2-(2-methylpyrazolo[1,5-a]pyridin-4-yl)cyclopropyl]methyl}carbamate (4.80 g) was fractionated by supercritical fluid chromatography (instrument: Multigram II (manufactured by Mettler-Toledo), column: CHIRALPAK AD-HKG-010 (20 mm ID×250 mm L, manufactured by Dicel Chemical Industries, Ltd.), mobile phase: A) carbon dioxide 100%, B) methanol 100%, mixing ratio: A/B=900/100, flow rate: 50 mL/min, column temperature: 35° C., sample concentration: 10 mg/mL (methanol), injection volume: 2.5 mL). A fraction solution containing an optically active compound having a shorter retention time under the above-mentioned supercritical fluid chromatography conditions was concentrated to give the title compound (2.21 g, 99.9% ee). Enantiomer excess (ee) was measured using supercritical fluid chromatography (column: CHIRALPAK AD-H LA-145 (4.6 mm ID×250 mm L, manufactured by Dicel Chemical Industries, Ltd.), mobile phase: A) carbon dioxide 100%, B) methanol 100%, mixing ratio: A/B=900/100, flow rate: 2.35 mL/min, column temperature: 35° C., sample concentration: 0.5 mg/mL (methanol), injection volume: 5 μL).

Workup

  1. additionA fraction solution containing an optically active compound
  2. concentrationwas concentrated

Sources & evidence

ORD record
ord-3e799b3f2d5642df872ad9dd35674ab6
Source dataset
uspto-grants-2012_02
Patent number
US08110585B2

Reaction notes

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