Sulfuric acid magnesium salt (1:1) → HCID 66972332, compound

HRID 1367828Notes

Reaction equation

HRID 1367828 reaction equation
[NH2:1][C@@H:2]([CH2:7][CH2:8][S:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][N:11]=1)[C:3]([O:5][CH3:6])=[O:4].[F:16][C:17]([F:28])([F:27])[C:18]([C:20]1[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=1)=O.CCN(C(C)C)C(C)C.C([BH3-])#N.[Na+].[O-]S([O-])(=O)=O.[Mg+2]>C(Cl)Cl.CO.C(OCC)(=O)C.Cl[Ti](Cl)(Cl)Cl>[CH3:6][O:5][C:3](=[O:4])[C@@H:2]([NH:1][CH:18]([C:20]1[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=1)[C:17]([F:16])([F:28])[F:27])[CH2:7][CH2:8][S:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][N:11]=1

Participants

10

Reactant 5

HCID 24083Sulfuric acid magnesium salt (1:1)HCID 695642,2,2,4'-TetrafluoroacetophenoneHCID 81531DiisopropylethylamineHCID 5003444Sodium cyanoborohydrideHCID 66972614HCID 66972614, compound

Product 1

HCID 66972332HCID 66972332, compound

Reagents, catalysts & solvents 4

HCID 24193Titanium TetrachlorideCatalystHCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

Methyl 2(S)-amino-4-(pyridin-2-ylsulfanyl)butyrate (0.610 g, 2.33 mmol), 2,2,2,4′-tetrafluoroacetophenone (0.393 g, 2.05 mmol), and DIPEA (1.24 g, 9.63 mmol) were combined in CH2Cl2 (10 mL). TiCl4 (1.90 mmol in CH2Cl2) was added dropwise over a 5 min period. The resulting dark solution was stirred for 3 h at which time sodium cyanoborohydride (6.35 mmol) in methanol (5 mL) was added in one portion, and the brown solution stirred for an additional 45 min. The reaction mixture was diluted with ethyl acetate, poured onto a bed of MgSO4 and filtered. Concentration and purification by flash chromatography (50% ethyl acetate/hexanes) afforded 4-(pyridin-2-ylsulfanyl)-2(S)-[2,2,2-trifluoro-1-(4-fluorophenyl)ethylamino]-butyric acid methyl ester as a mixture of diastereomers.

Workup

  1. additionwas added in one portion
  2. filtrationfiltered
  3. concentrationConcentration and purification by flash chromatography (50% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-1246c6cbdbdc4340af0a2fcb70eee676
Source dataset
uspto-grants-2011_02
Patent number
US07893093B2

Reaction notes

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