Sodium Hydroxide → Trifluoroacetic acid

HRID 1485841Notes

Reaction equation

HRID 1485841 reaction equation
[CH3:1][O:2][C:3]1[CH:20]=[CH:19][C:6]([CH2:7][N:8]2[C:12]([C:13]([OH:15])=[O:14])=[CH:11][C:10]([C:16]([OH:18])=O)=[N:9]2)=[CH:5][CH:4]=1.CN(C([O:28]N1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C([O:47][C:48](=[O:64])[C@H:49]([OH:63])[C@H:50]([NH2:62])[CH2:51][C:52]1[CH:57]=[CH:56][CH:55]=[CH:54][C:53]=1[C:58]([F:61])([F:60])[F:59])C.CCN(C(C)C)C(C)C.[OH-:74].[Na+]>CN(C=O)C.CCO.CC(O)=O>[C:48]([C@H:49]([OH:63])[C@H:50]([NH:62][C:16]([C:10]1[CH:11]=[C:12]([C:13]([OH:15])=[O:14])[N:8]([CH2:7][C:6]2[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:20][CH:19]=2)[N:9]=1)=[O:18])[CH2:51][C:52]1[CH:57]=[CH:56][CH:55]=[CH:54][C:53]=1[C:58]([F:60])([F:61])[F:59])([OH:64])=[O:47].[C:53]([OH:28])([C:58]([F:61])([F:60])[F:59])=[O:74]

Participants

10

Reactant 5

HCID 14798Sodium HydroxideHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 71073550(2R,3R)-3-amino-2-hydroxy-4-(2-trifluoromethyl-phenyl)-butyric acid ethyl esterHCID 710741191-(4-Methoxybenzyl)-1H-pyrazole-3,5-dicarboxylic Acid

Product 2

HCID 6422Trifluoroacetic acidYield 95%HCID 710741415-[(1R,2R)-2-Carboxy-2-hydroxy-1-(2-trifluoromethylbenzyl)-ethylcarbamoyl]-2-(4-methoxybenzyl)-2H-pyrazole-3-carboxylic Acid

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 702EthanolSolventHCID 6228DimethylformamideSolvent

Procedure

1-(4-Methoxybenzyl)-1H-pyrazole-3,5-dicarboxylic acid (63.8 mg, 231 μmol, 1.0 eq.), HATU (88 mg, 230 μmol, 1.0 eq.), and (2R,3R)-3-amino-2-hydroxy-4-(2-trifluoromethyl-phenyl)-butyric acid ethyl ester (67.3 mg, 231 μmol, 1.0 eq.) were dissolved in DMF (5 mL) and stirred at room temperature for 2 minutes. DIPEA (121 μL, 3.0 eq.) was added and the mixture was stirred for 1 hour. The crude material was then dissolved in EtOH, and enough equivalents of 10N NaOH were added to make the solution basic. The reaction was monitored for 1 hour until completion. The solution was re-acidified with an equal volume of AcOH and vacuumed to dryness. The product was purified by preparative HPLC to yield the title compound as a TFA salt (12 mg, 95% purity). MS m/z [M+H]+ calc'd for C24H22F3N3O7, 522.14. found 522.2.

Workup

  1. stirringthe mixture was stirred for 1 hour
  2. waitThe reaction was monitored for 1 hour until completion
  3. customThe product was purified by preparative HPLC

Sources & evidence

ORD record
ord-60f0365392fe464dbe5c12297edc5f47
Source dataset
uspto-grants-2016_08
Patent number
US09422245B2

Reaction notes

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