Lithium Hydroxide → 1-methyl-L-prolyl-N1-[(1S,2E)-3-carboxy-1-isopropylbut-2-enyl]-N1,3-dimethyl-L-valinamide

HRID 133814Notes

Reaction equation

HRID 133814 reaction equation
O.[CH3:2][N:3]1[CH2:10][CH2:9][CH2:8][C@H:4]1[C:5]([OH:7])=O.F[P-](F)(F)(F)(F)F.N1(O[P+](N2CCCC2)(N2CCCC2)N2CCCC2)C2C=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C.[CH3:53]/[C:54](=[CH:60]\[C@@H:61]([N:65]([CH3:74])[C:66](=[O:73])[C@H:67]([C:69]([CH3:72])([CH3:71])[CH3:70])[NH2:68])[CH:62]([CH3:64])[CH3:63])/[C:55]([O:57]CC)=[O:56].[OH-].[Li+]>ClCCl.CO.ClCCl.O.O1CCCC1.O>[CH3:2][N:3]1[CH2:10][CH2:9][CH2:8][C@H:4]1[C:5]([NH:68][C@H:67]([C:66]([N:65]([C@@H:61]([CH:62]([CH3:64])[CH3:63])/[CH:60]=[C:54](/[C:55]([OH:57])=[O:56])\[CH3:53])[CH3:74])=[O:73])[C:69]([CH3:71])([CH3:72])[CH3:70])=[O:7]

Participants

11

Reactant 5

HCID 3939Lithium HydroxideHCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 11120545ethyl (2E,4S)-2,5-dimethyl-4-[methyl(3-methyl-L-valyl)amino]hex-2-enoateHCID 162119581-Methyl-L-proline--water (1/1)

Product 1

HCID 115963751-methyl-L-prolyl-N1-[(1S,2E)-3-carboxy-1-isopropylbut-2-enyl]-N1,3-dimethyl-L-valinamideYield 28%

Reagents, catalysts & solvents 5

HCID 887MethanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolventHCID 21908982Water methylene chlorideSolvent

Procedure

To a solution of N-methyl-L-proline monohydrate (0.26 g, 1.79 mmol) and benzotriazole-1-yl-oxy-tris-pyrrolidinophosphonium hexafluorophosphate (1.4 g, 2.69 mmol) in anhydrous dichloromethane (3.0 ml) at 25° C. is added diisopropylethylamine (0.63 ml, 3.62 mmol) under an inert atmosphere. To this solution is added a solution of ethyl (2E,4S)-2,5-dimethyl-4-[methyl(3-methyl-L-valyl)amino]hex-2-enoate (0.39 g, 1.27 mmol, WO 99/32509) in anhydrous dichloromethane (2.0 ml). The resulting reaction mixture is stirred at room temperature overnight. The reaction mixture is evaporated in vacuo. The residue (300 mg, 0.78 mmol) is dissolved in methanol (6.85 ml), water (1.8 ml) and tetrahydrofuran (3.25 ml). To this reaction mixture is added aqueous lithium hydroxide solution (3.54 ml, 3.54 mol) The resulting mixture is stirred at room temperature overnight. The reaction mixture is diluted with dichloromethane/water. The organic layer is washed with citric acid, brine, dried over sodium sulfate and filtered. The solvent is removed in vacuo, and the residue is chromatographed by HPLC (0.01% trifluoroacetic acid in water/acetonitrile) to give the product as a yellow oil, 0.08 g (28% yield). MS: m/z 396.28 (M+1)

Workup

  1. customThe resulting reaction mixture
  2. customThe reaction mixture is evaporated in vacuo
  3. stirringis stirred at room temperature overnight
  4. washThe organic layer is washed with citric acid, brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. customThe solvent is removed in vacuo
  8. customthe residue is chromatographed by HPLC (0.01% trifluoroacetic acid in water/acetonitrile)

Sources & evidence

ORD record
ord-59ee916141ad46738b2af49d26046a88
Source dataset
uspto-grants-2008_06
Patent number
US07390910B2

Reaction notes

Loading…