Acetone → Hydrochloric Acid

HRID 516454Notes

Reaction equation

HRID 516454 reaction equation
CCN(CC)CC.[Cl:8][C:9]1[CH:10]=[C:11]([C:15]2[CH:20]=[CH:19][C:18]([CH2:21][C@@H:22]([NH:29][C:30]([C:32]3[CH:41]=[CH:40][C:35]4[N:36]=[N:37][N:38]([OH:39])[C:34]=4[CH:33]=3)=[O:31])[CH2:23][C@@H:24]([OH:28])[C:25]([OH:27])=[O:26])=[CH:17][CH:16]=2)[CH:12]=[CH:13][CH:14]=1.[Cl:42][CH2:43][O:44][C:45](=[O:58])[C@@H:46]([NH:50]C(OC(C)(C)C)=O)[CH:47]([CH3:49])[CH3:48].CC(C)=O.C(O)(C(F)(F)F)=O.C(Cl)Cl>>[NH2:50][C@H:46]([CH:47]([CH3:49])[CH3:48])[C:45]([O:44][CH2:43][O:39][N:38]1[C:34]2[CH:33]=[C:32]([C:30]([NH:29][C@H:22]([CH2:21][C:18]3[CH:17]=[CH:16][C:15]([C:11]4[CH:12]=[CH:13][CH:14]=[C:9]([Cl:8])[CH:10]=4)=[CH:20][CH:19]=3)[CH2:23][C@@H:24]([OH:28])[C:25]([OH:27])=[O:26])=[O:31])[CH:41]=[CH:40][C:35]=2[N:36]=[N:37]1)=[O:58].[ClH:42]

Participants

7

Reactant 5

HCID 180AcetoneHCID 8471TriethylamineHCID 21863450Trifluoroacetic acid methylene chlorideHCID 54112037chloromethyl (2S)-2-(((tert-butoxy)carbonyl)amino)-3-methylbutanoateHCID 67970017(2R,4R)-5-(3'-Chlorobiphenyl-4-yl)-2-hydroxy-4-[(3-hydroxy-3H-benzotriazole-5-carbonyl)amino]pentanoic Acid

Product 2

HCID 313Hydrochloric AcidYield 404.9%HCID 86705146HCID 86705146, compound

Conditions

Temperature
65 °C

Procedure

Et3N (7.0 μL, 50 μmol) was added to a solution of [(2R,4R)-5-(3′-chlorobiphenyl-4-yl)-2-hydroxy-4-[(3-hydroxy-3H-benzotriazole-5-carbonyl)amino]pentanoic acid (20.0 mg, 42 μmol) and (S)-2-t-butoxycarbonylamino-3-methylbutyric acid chloromethyl ester (17.7 mg, 67 μmol) in acetone (1.3 mL, 17.2 mmol), and the resulting mixture was stirred in a sealed vial at 65° C. for 5 hours. 1:1 TFA/DCM (0.50 mL, 3.1 mmol) was added, and the mixture was stirred at room temperature for 30 minutes and concentrated to yield a clear yellow liquid. The crude liquid was purified by preparative HPLC (C18 column chromatography, small column, using 30-90% MeCN in water with 0.05% TFA) to yield the title compound as a white solid HCl salt (6.2 mg, purity 96%). MS m/z [M+H]+ calc'd for C30H32ClN5O7, 610.20. found 610.1.

Workup

  1. stirringthe mixture was stirred at room temperature for 30 minutes
  2. concentrationconcentrated
  3. customto yield a clear yellow liquid
  4. customThe crude liquid was purified by preparative HPLC (C18 column chromatography, small column, using 30-90% MeCN in water with 0.05% TFA)

Sources & evidence

ORD record
ord-1dde61ae5a3b4354b742e2211f4158db
Source dataset
uspto-grants-2015_08
Patent number
US09108934B2

Reaction notes

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