Isopropanol → tert-butyl {[(1S,2S)-2-(5-fluoro-2-methyl-2H-indazol-4-yl)cyclopropyl]methyl}carbamate

HRID 1639861Notes

Reaction equation

HRID 1639861 reaction equation
[C:1]([O:5][C:6](=[O:23])[NH:7][CH2:8][C@@H:9]1[CH2:11][C@H:10]1[C:12]1[C:13]2[C:17]([CH:18]=[CH:19][C:20]=1[F:21])=[N:16][N:15]([CH3:22])[CH:14]=2)([CH3:4])([CH3:3])[CH3:2].CC(NCCC#N)CC1C=CC=CC=1.Cl.CCCCCC.CC(O)C>CCCCCC.CC(O)C>[C:1]([O:5][C:6](=[O:23])[NH:7][CH2:8][C@H:9]1[CH2:11][C@@H:10]1[C:12]1[C:13]2[C:17]([CH:18]=[CH:19][C:20]=1[F:21])=[N:16][N:15]([CH3:22])[CH:14]=2)([CH3:3])([CH3:4])[CH3:2]

Participants

6

Reactant 4

HCID 3776IsopropanolHCID 8058HexaneHCID 161245Fenproporex hydrochlorideHCID 59334581tert-butyl {[(1R,2R)-2-(5-fluoro-2-methyl-2H-indazol-4-yl)cyclopropyl]methyl)carbamate

Product 1

HCID 59334635tert-butyl {[(1S,2S)-2-(5-fluoro-2-methyl-2H-indazol-4-yl)cyclopropyl]methyl}carbamateYield 48%

Reagents, catalysts & solvents 1

HCID 21585144Isopropanol hexaneSolvent

Procedure

Trans-tert-butyl{[2-(5-fluoro-2-methyl-2H-indazol-4-yl)cyclopropyl]methyl}carbamate (735 mg) was fractionated by high performance liquid chromatography (instrument: K-Prep (manufactured by YMC), column: CHIRALPAK AS (50 mm ID×500 mm L, manufactured by Dicel Chemical Industries, Ltd.), mobile phase: A) hexane 100%, B) 2-propanol 100%, mixing ratio: A/B=900/100, flow rate: 80 mL/min, column temperature: 25° C., sample concentration: 21 mg/mL (hexane/2-propanol=900/100), injection amount: 735 mg). A fraction solution containing an optically active compound having a longer retention time under the above-mentioned high performance liquid chromatography conditions was concentrated to give the title compound (353 mg, 99.9% ee). Enantiomer excess (ee) was measured by high performance liquid chromatography (column: CHIRALPAK AS (4.6 mm ID×250 mm L, manufactured by Dicel Chemical Industries, Ltd.), mobile phase: hexane/2-propanol=90/10, flow rate: 1.0 mL/min, column temperature: 30° C., sample concentration: 0.5 mg/mL (hexane/2-propanol=90/10), injection volume: 10 μL).

Workup

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

Sources & evidence

ORD record
ord-b1a9534e2c3b4318a0c6cf5e3e1ccc20
Source dataset
uspto-grants-2012_02
Patent number
US08110585B2

Reaction notes

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