Hexane → N''-[N-METHOXYCARBONYL-L-VALYL]-N-[(S)-3,3,3-TRIFLUOR-1-ISOPROPYL-2-OXOPROPYL]-L-PROLINAMIDE

HRID 2393804Notes

Reaction equation

HRID 2393804 reaction equation
[Mn]([O-])(=O)(=O)=O.[K+].[CH3:7][O:8][C:9]([NH:11][C@@H:12]([CH:33]([CH3:35])[CH3:34])[C:13]([N:15]1[CH2:19][CH2:18][CH2:17][C@H:16]1[C:20]([NH:22][C@H:23]([C@@H:27]([OH:32])[C:28]([F:31])([F:30])[F:29])[CH:24]([CH3:26])[CH3:25])=[O:21])=[O:14])=[O:10].[OH-].[Na+].CCCCCC>O.C(O)(C)(C)C.C(OCC)(=O)C>[CH3:7][O:8][C:9]([NH:11][C@@H:12]([CH:33]([CH3:35])[CH3:34])[C:13]([N:15]1[CH2:19][CH2:18][CH2:17][C@H:16]1[C:20]([NH:22][C@H:23]([C:27](=[O:32])[C:28]([F:31])([F:30])[F:29])[CH:24]([CH3:26])[CH3:25])=[O:21])=[O:14])=[O:10]

Participants

8

Reactant 4

HCID 8058Hexane2×HCID 14798Sodium HydroxideHCID 516875Potassium PermanganateHCID 15850445HCID 15850445, compound

Product 1

HCID 9910174N''-[N-METHOXYCARBONYL-L-VALYL]-N-[(S)-3,3,3-TRIFLUOR-1-ISOPROPYL-2-OXOPROPYL]-L-PROLINAMIDEYield 63.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 6386tert-ButanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of potassium permanganate (16.6 g) in water (100 ml) was added dropwise to a 0° C. solution of (S)-1-[(S)-2-(methoxycarbonylamino)-3-methylbutyryl]-N-[(S)-2-methyl-1-((R)-2,2,2-trifluoro-1-hydroxyethyl)propyl]pyrrolidine-2-carboxamide (15 g) in tert-butyl alcohol (175 ml), water (100 ml), and 0.6M sodium hydroxide solution (175 ml). The solution was stirred for 2 hours and then quenched by addition of methanol (70 ml), followed by stirring for 1 hour. The mixture was filtered through diatomaceous earth and the filtrate made acidic to pH 2 using 1M hydrochloric acid, and saturated with sodium chloride. The product was extracted into ether (5×100 ml) and the solvent removed under vacuum. The resulting oil was chromatographed (methanol: dichloromethane 5:95) and the solvent removed to give an oil. Hexane (40 ml) was added to a stirred solution of the oil in ethyl acetate (which had been presaturated with water) (40 ml) and stirring was continued for 24 hours over which time a crystalline solid formed. Another portion of hexane (40 ml) was added and the solid was collected and dried under vacuum (40° C.) to give (S)-1-[(S)-2-(methoxycarbonylamino)-3-methylbutyryl]-N-[(S)-2-methyl-1-(2,2,2-trifluoroacetyl)propyl]-pyrrolidine-2-carboxamide (9.45 g) as a white crystalline solid (as substantially or essentially Form A); 1H NMR (300 MHz, DMSO/D2O): 4.42 (m, 1H) 4.02 (d, 1H), 3.73 (m, 1H), 3.59 (m, 1H), 3.54 (s, 3H), 2.23 (m, 1H), 2.00-1.76 (m, 6H), 0.91 (m, 6H), 0.85 (d, 3H), 0.80 (d, 3H); Analysis for C18H28F3N3 O5.H2O: Calculated; C, 48.97; H, 6.85; N, 9.51; Found: C, 49.02, H, 6.80; N, 9.66; (XDS shown in FIG. 1).

Workup

  1. customquenched by addition of methanol (70 ml)
  2. stirringby stirring for 1 hour
  3. filtrationThe mixture was filtered through diatomaceous earth
  4. extractionThe product was extracted into ether (5×100 ml)
  5. customthe solvent removed under vacuum
  6. customThe resulting oil was chromatographed (methanol: dichloromethane 5:95)
  7. customthe solvent removed
  8. customto give an oil
  9. stirringstirring
  10. waitwas continued for 24 hours over which time
  11. customa crystalline solid formed
  12. customthe solid was collected
  13. customdried under vacuum (40° C.)

Sources & evidence

ORD record
ord-6494fb3289a44d42a254f0b15414c390
Source dataset
uspto-grants-1998_09
Patent number
US05808097

Reaction notes

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