(S)-tert-Butyl (2-oxopyrrolidin-3-yl)carbamate → [1(-3-Amino-4-cyanobenzyl)-2-oxopyrrolidin-3-(S)-yl]carbamic acid tert-butyl ester

HRID 651685Notes

Reaction equation

HRID 651685 reaction equation
[C:1]([O:5][C:6](=[O:14])[NH:7][C@H:8]1[CH2:12][CH2:11][NH:10][C:9]1=[O:13])([CH3:4])([CH3:3])[CH3:2].CC(C)([O-])C.[K+].[NH2:21][C:22]1[CH:29]=[C:28]([CH2:30]Br)[CH:27]=[CH:26][C:23]=1[C:24]#[N:25]>C1COCC1.C1OCCOCCOCCOCCOCCOC1>[C:1]([O:5][C:6](=[O:14])[NH:7][C@H:8]1[CH2:12][CH2:11][N:10]([CH2:30][C:28]2[CH:27]=[CH:26][C:23]([C:24]#[N:25])=[C:22]([NH2:21])[CH:29]=2)[C:9]1=[O:13])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 3

HCID 10750535(S)-tert-Butyl (2-oxopyrrolidin-3-yl)carbamateHCID 217084862-Amino-4-(bromomethyl)benzonitrileHCID 23665647Potassium tert-butoxide

Product 1

HCID 70121975[1(-3-Amino-4-cyanobenzyl)-2-oxopyrrolidin-3-(S)-yl]carbamic acid tert-butyl esterYield 75%

Reagents, catalysts & solvents 2

HCID 2855718-Crown-6CatalystHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

(2-Oxopyrrolidin-3-(S)-yl) carbamic acid tert-butyl ester (1 g, 5 mmol) is dissolved in THF (100 mL) under nitrogen, and cooled to 0° C. Potassium-tert-butoxide (0.62 g, 5.5 mmol) is added in one portion to the vigorously stirring solution, followed by 18-crown-6 (10 mg, 0.038 mmol), and the reaction mixture allowed to warm to room temperature and stirred for 1 hour. The solution is cooled to 0° C. and 2-amino-4-(bromomethyl)benzonitrile (1.16 g, 5.5 mmol) added dropwise as a solution in THF (10 mL), before leaving the reaction mixture to warm to room temperature and stir overnight. The reaction is quenched with 0.25M HCl (20 mL), then neutralized with saturated aqueous NaHCO3, and brine added. The solution is extracted with ethyl acetate, and the organic phase dried over MgSO4, concentrated, and purified by column chromatograph on silica with 0.5-5% methanol/dichloromethane. The product fractions are combined, concentrated, and the semi-solid oily residue triturated with hexanes/dichloromethane=100/1 (25 mL). The product is isolated as a pale yellow powder (1.24 g, 3.75 mmol).

Workup

  1. temperatureto warm to room temperature
  2. temperatureThe solution is cooled to 0° C.
  3. custombefore leaving the reaction mixture
  4. temperatureto warm to room temperature
  5. stirringstir overnight
  6. customThe reaction is quenched with 0.25M HCl (20 mL)
  7. additionadded
  8. extractionThe solution is extracted with ethyl acetate
  9. dry with materialthe organic phase dried over MgSO4
  10. concentrationconcentrated
  11. custompurified by column chromatograph on silica with 0.5-5% methanol/dichloromethane
  12. concentrationconcentrated
  13. customthe semi-solid oily residue triturated with hexanes/dichloromethane=100/1 (25 mL)

Sources & evidence

ORD record
ord-305ef8dfebe54a1ea9274ab0b6047a15
Source dataset
uspto-grants-2001_08
Patent number
US06281227B1

Reaction notes

Loading…