Trifluoroacetic acid → (2S,4S,5S)-5-Amino-6-[4-(2-chloro-5-fluorophenyl)-2,2-dimethyl-5-oxopiperazin-1-yl]-4-hydroxy-2-isopropylhexanoic acid butylamide fumarate

HRID 1694936Notes

Reaction equation

HRID 1694936 reaction equation
FC(F)(F)C(O)=O.C(OC(=O)[NH:14][C@@H:15]([CH2:30][N:31]1[CH2:36][C:35](=[O:37])[N:34]([C:38]2[CH:43]=[C:42]([F:44])[CH:41]=[CH:40][C:39]=2[Cl:45])[CH2:33][C:32]1([CH3:47])[CH3:46])[C@@H:16]([OH:29])[CH2:17][C@H:18]([C:22](=[O:28])[NH:23][CH2:24][CH2:25][CH2:26][CH3:27])[CH:19]([CH3:21])[CH3:20])(C)(C)C.[C:49]([OH:56])(=[O:55])/[CH:50]=[CH:51]/[C:52]([OH:54])=[O:53].C(NC(=O)[C@H](C(C)C)C[C@H](O)[C@@H](N)CN1CC(=O)N(C2C=C(F)C=CC=2Cl)CC1(C)C)CCC>C(Cl)Cl.CO>[C:49]([OH:56])(=[O:55])/[CH:50]=[CH:51]/[C:52]([OH:54])=[O:53].[CH2:24]([NH:23][C:22](=[O:28])[C@H:18]([CH:19]([CH3:21])[CH3:20])[CH2:17][C@H:16]([OH:29])[C@@H:15]([NH2:14])[CH2:30][N:31]1[CH2:36][C:35](=[O:37])[N:34]([C:38]2[CH:43]=[C:42]([F:44])[CH:41]=[CH:40][C:39]=2[Cl:45])[CH2:33][C:32]1([CH3:46])[CH3:47])[CH2:25][CH2:26][CH3:27]

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 444972Fumaric AcidHCID 24966529(2S,4S,5S)-5-amino-6-[4-(2-chloro-5-fluorophenyl)-2,2-dimethyl-5-oxopiperazin-1-yl]-4-hydroxy-2-isopropylhexanoic acid butylamideHCID 66645473{(1S,2S,4S)-4-Butylcarbamoyl-1-[4-(2-chloro-5-fluorophenyl)-2,2-dimethyl-5-oxopiperazin-1-ylmethyl]-2-hydroxy-5-methylhexyl}carbamic acid t-butyl ester

Product 1

HCID 60204009(2S,4S,5S)-5-Amino-6-[4-(2-chloro-5-fluorophenyl)-2,2-dimethyl-5-oxopiperazin-1-yl]-4-hydroxy-2-isopropylhexanoic acid butylamide fumarateYield 87%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

0.98 ml of trifluoroacetic acid (12.7 mmol) was added to a solution of 254 mg of {(1S,2S,4S)-4-butylcarbamoyl-1-[4-(2-chloro-5-fluorophenyl)-2,2-dimethyl-5-oxopiperazin-1-ylmethyl]-2-hydroxy-5-methylhexyl}carbamic acid t-butyl ester obtained in Example (62g) (0.42 mmol) in methylene chloride (1.9 ml) at room temperature, and the mixture was stirred at the same temperature for 30 minutes. The reaction mixture was concentrated under reduced pressure and diluted with a saturated sodium bicarbonate aqueous solution, 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). 49 mg of fumaric acid (0.42 mmol) was added to a solution of 207 mg of (2S,4S,5S)-5-amino-6-[4-(2-chloro-5-fluorophenyl)-2,2-dimethyl-5-oxopiperazin-1-yl]-4-hydroxy-2-isopropylhexanoic acid butylamide obtained above (0.42 mmol) in methanol (4 ml), and the mixture was stirred at room temperature for five minutes. The solvent was evaporated under reduced pressure to obtain 220 mg of the title compound (yield: 87%).

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. additiondiluted with a saturated sodium bicarbonate aqueous solution
  3. extractionfollowed by extraction with methylene chloride
  4. dry with materialThen, the organic layer was dried over anhydrous magnesium sulfate
  5. filtrationAfter filtration
  6. customthe solvent was evaporated under reduced pressure
  7. customthe residue was purified by silica gel column chromatography (elution solvent:methylene chloride/methanol/triethylamine=100/10/1)
  8. stirringthe mixture was stirred at room temperature for five minutes
  9. customThe solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-adb6449f1e7e4107855d94fb4bc28528
Source dataset
uspto-grants-2012_04
Patent number
US08158790B2

Reaction notes

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