Hydrochloric Acid → (2S,4S,5S)-5-Amino-6-[4-(2-chlorophenyl)-2,2-dimethyl-5-oxopiperazin-1-yl]-4-hydroxy-2-isopropylhexanoic acid [(S)-2-methylbutyl]amide fumarate

HRID 1694898Notes

Reaction equation

HRID 1694898 reaction equation
Cl.C(OC(=O)[NH:8][C@@H:9]([CH2:25][N:26]1[CH2:31][C:30](=[O:32])[N:29]([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=2[Cl:39])[CH2:28][C:27]1([CH3:41])[CH3:40])[C@@H:10]([OH:24])[CH2:11][C@H:12]([C:16](=[O:23])[NH:17][CH2:18][C@@H:19]([CH3:22])[CH2:20][CH3:21])[CH:13]([CH3:15])[CH3:14])(C)(C)C.C(=O)(O)[O-].[Na+].[C:48]([OH:55])(=[O:54])/[CH:49]=[CH:50]/[C:51]([OH:53])=[O:52].C[C@@H](CC)CNC(=O)[C@H](C(C)C)C[C@H](O)[C@@H](N)CN1CC(=O)N(C2C=CC=CC=2Cl)CC1(C)C>O1CCOCC1.CO>[C:48]([OH:55])(=[O:54])/[CH:49]=[CH:50]/[C:51]([OH:53])=[O:52].[CH3:22][C@@H:19]([CH2:20][CH3:21])[CH2:18][NH:17][C:16](=[O:23])[C@H:12]([CH:13]([CH3:14])[CH3:15])[CH2:11][C@H:10]([OH:24])[C@@H:9]([NH2:8])[CH2:25][N:26]1[CH2:31][C:30](=[O:32])[N:29]([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=2[Cl:39])[CH2:28][C:27]1([CH3:41])[CH3:40]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 444972Fumaric AcidHCID 516892Sodium BicarbonateHCID 24968904(2S,4S,5S)-5-amino-6-[4-(2-chlorophenyl)-2,2-dimethyl-5-oxopiperazin-1-yl]-4-hydroxy-2-isopropylhexanoic acid [(S)-2-methylbutyl]amideHCID 66645798{(1S,2S,4S)-1-[4-(2-Chlorophenyl)-2,2-dimethyl-5-oxopiperazin-1-ylmethyl]-2-hydroxy-5-methyl-4-[(S)-2-methylbutylcarbamoyl]hexyl}carbamic acid t-butyl ester

Product 1

HCID 66645822(2S,4S,5S)-5-Amino-6-[4-(2-chlorophenyl)-2,2-dimethyl-5-oxopiperazin-1-yl]-4-hydroxy-2-isopropylhexanoic acid [(S)-2-methylbutyl]amide fumarateYield 75.7%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 312751,4-DioxaneSolvent2×

Procedure

2.3 ml of a solution of 4 N hydrochloric acid in dioxane (9.3 mmol) was added to a solution of 184 mg of {(1S,2S,4S)-1-[4-(2-chlorophenyl)-2,2-dimethyl-5-oxopiperazin-1-ylmethyl]-2-hydroxy-5-methyl-4-[(S)-2-methylbutyl]hexyl}carbamic acid t-butyl ester obtained in Example (2a) (0.31 mmol) in dioxane (0.3 ml) at room temperature, and the mixture was stirred at the same temperature for 15 minutes. A saturated sodium bicarbonate aqueous solution was added to the reaction mixture under cooling in an ice bath, followed by extraction with methylene chloride. Then, the organic layer was dried over anhydrous magnesium sulfate. After filtration, the solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (elution solvent:methylene chloride/methanol/triethylamine=100/10/1). 17.6 mg of fumaric acid (0.24 mmol) was added to a solution of 118 mg of (2S,4S,5S)-5-amino-6-[4-(2-chlorophenyl)-2,2-dimethyl-5-oxopiperazin-1-yl]-4-hydroxy-2-isopropylhexanoic acid [(S)-2-methylbutyl]amide obtained above (0.24 mmol) in methanol (2.4 ml), and the mixture was stirred at room temperature for five minutes. The solvent was evaporated under reduced pressure to obtain 111 mg of the title compound (yield: 59%).

Workup

  1. temperatureunder cooling in an ice bath
  2. extractionfollowed by extraction with methylene chloride
  3. dry with materialThen, the organic layer was dried over anhydrous magnesium sulfate
  4. filtrationAfter filtration
  5. customthe solvent was evaporated under reduced pressure
  6. customthe residue was purified by silica gel column chromatography (elution solvent:methylene chloride/methanol/triethylamine=100/10/1)
  7. stirringthe mixture was stirred at room temperature for five minutes
  8. customThe solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-c653725a3fd2468ebab783547e03d987
Source dataset
uspto-grants-2012_04
Patent number
US08158790B2

Reaction notes

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