Hydrochloric Acid → (S)-1-((R)-2-Hydroxy-3,3-dimethyl-butyryl)-pyrrolidine-2-carboxylic acid 2-aminomethyl-5-chloro-benzylamide

HRID 1058279Notes

Reaction equation

HRID 1058279 reaction equation
[CH3:1][C:2]([CH3:33])([CH3:32])[C@@H:3]([OH:31])[C:4]([N:6]1[CH2:30][CH2:29][CH2:28][C@H:7]1[C:8]([NH:10][CH2:11][C:12]1[CH:17]=[C:16]([Cl:18])[CH:15]=[CH:14][C:13]=1[CH2:19][NH:20]C(OC(C)(C)C)=O)=[O:9])=[O:5].Cl>C(Cl)Cl.CCOCC>[CH3:1][C:2]([CH3:33])([CH3:32])[C@@H:3]([OH:31])[C:4]([N:6]1[CH2:30][CH2:29][CH2:28][C@H:7]1[C:8]([NH:10][CH2:11][C:12]1[CH:17]=[C:16]([Cl:18])[CH:15]=[CH:14][C:13]=1[CH2:19][NH2:20])=[O:9])=[O:5]

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 113061991-((2R)-3,3-dimethyl-2-hydroxybutanoyl)-N-(2-(tert-butyloxycarbonylaminomethyl)-5-chlorobenzyl)-L-prolinamide

Product 1

HCID 11740591(S)-1-((R)-2-Hydroxy-3,3-dimethyl-butyryl)-pyrrolidine-2-carboxylic acid 2-aminomethyl-5-chloro-benzylamide

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

1-((2R)-3,3-Dimethyl-2-hydroxybutanoyl)-N-(2-(tert-butyloxycarbonylaminomethyl)-5-chlorobenzyl)-L-prolinamide from the previous step (4.65 g, 9.65 mmol, HPLC RT=3.35 min) was dissolved in CH2Cl2 (15 mL) and cooled with stirring to 0° C. A solution of anhydrous HCl in ether (38 mL of a 1 Molar solution, 38 mmol) was added slowly. The resulting solution was stirred at 0° C. for 10 min, and then at ambient temperature for 20 h. The solid which had formed was collected by filtration and washed with several portions of ether. The solid was purified by preparative reverse-phase HPLC using an acetonitrile:water gradient containing 0.05% concentrated HCl. The product-containing fractions were combined and lyophilized to give the hydrochloride salt of the title compound as a white solid (HPLC RT=2.52 min, method A; LC-MS m/z=382; C, H, N combustion analysis, calculated for C19H28ClN3O3, 1.0HCl, 1.5H2O, calculated C, 51.24, H, 7.24, N, 9.43, found C, 51.32, H, 7.17, B, 9.33).

Workup

  1. temperaturecooled
  2. stirringThe resulting solution was stirred at 0° C. for 10 min
  3. customThe solid which had formed
  4. filtrationwas collected by filtration
  5. washwashed with several portions of ether
  6. customThe solid was purified by preparative reverse-phase
  7. additionwater gradient containing 0.05% concentrated HCl

Sources & evidence

ORD record
ord-f949b0d351d94e6f863acd00f6d3537a
Source dataset
uspto-grants-2003_02
Patent number
US06515011B2

Reaction notes

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