Hydrochloric Acid → (R)-1-(4-chlorobenzyl)-3-(glycylamino)pyrrolidine

HRID 279254Notes

Reaction equation

HRID 279254 reaction equation
C(OC([NH:8][CH2:9][C:10]([NH:12][C@@H:13]1[CH2:17][CH2:16][N:15]([CH2:18][C:19]2[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][CH:20]=2)[CH2:14]1)=[O:11])=O)(C)(C)C.Cl>CO.O1CCOCC1>[NH2:8][CH2:9][C:10]([NH:12][C@@H:13]1[CH2:17][CH2:16][N:15]([CH2:18][C:19]2[CH:20]=[CH:21][C:22]([Cl:25])=[CH:23][CH:24]=2)[CH2:14]1)=[O:11]

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 53939240(R)-3-(N-(tert-butoxycarbonyl)glycyl)amino-1-(4-chlorobenzyl)pyrrolidine

Product 1

HCID 54551710(R)-1-(4-chlorobenzyl)-3-(glycylamino)pyrrolidineYield 86%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution of (R)-3-(N-(tert-butoxycarbonyl)glycyl)amino-1-(4-chlorobenzyl)pyrrolidine (5.39 g, 14.7 mmol) in methanol (60 mL) was added 4 N HCl in dioxane (38 mL). The solution was stirred at room temperature for 2 h. The reaction mixture was concentrated and 2 N NaOH solution (80 mL) was added. The mixture was extracted with dichloromethane (80 mL×3), and the combined extracts were dried over sodium sulfate and concentrated. Column chromatography (SiO2, AcOEt/EtOH/Et3N=90/5/5) gave (R)-3-(glycyl)amino-1-(4-chlorobenzyl)pyrrolidine (3.374 g, 86%): 1H NMR (CDCl3, 270 MHz) δ1.77 (dd, J=1.3 and 6.9 Hz, 1H), 2.20-3.39 (m, 2H), 2.53 (dd, J=3.3 and 9.6 Hz, 1H), 2.62 (dd, J=6.6 and 9.6 Hz, 1H), 2.78-2.87 (m, 1H), 3.31 (s, 2H), 3.57 (s, 2H), 4.38-4.53 (br, 1H), 7.18-7.32 (m, 4H), 7.39 (br. s, 1H).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. addition2 N NaOH solution (80 mL) was added
  3. extractionThe mixture was extracted with dichloromethane (80 mL×3)
  4. dry with materialthe combined extracts were dried over sodium sulfate
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-dc651c246da446ff9c553f221a9926d6
Source dataset
uspto-grants-2002_03
Patent number
US06362177B1

Reaction notes

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