Hydrochloric Acid → 2-(2-Oxo-3-benzyl-5-methyl-cyclohept-4-en-1-yl)-1-oxo-ethyl-valinyl valine methyl ester

HRID 1755808Notes

Reaction equation

HRID 1755808 reaction equation
[O:1]=[C:2]1[CH:8]([CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH:7]=[C:6]([CH3:16])[CH2:5][CH2:4][CH:3]1[CH2:17][C:18]([O:20]C)=O.O[Li].O.Cl.[NH2:26][C@H:27]([C:31]([NH:33][C@H:34]([C:38]([O:40][CH3:41])=[O:39])[CH:35]([CH3:37])[CH3:36])=[O:32])[CH:28]([CH3:30])[CH3:29].OC1C2N=NNC=2C=CC=1.CN([P+](ON1N=NC2C=CC=CC1=2)(N(C)C)N(C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.C(N(CC)CC)C.O.O1CCOCC1>[CH3:41][O:40][C:38](=[O:39])[C@H:34]([CH:35]([CH3:37])[CH3:36])[NH:33][C:31](=[O:32])[C@H:27]([CH:28]([CH3:29])[CH3:30])[NH:26][C:18](=[O:20])[CH2:17][CH:3]1[CH2:4][CH2:5][C:6]([CH3:16])=[CH:7][CH:8]([CH2:9][C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=2)[C:2]1=[O:1]

Participants

11

Reactant 6

HCID 313Hydrochloric AcidHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 168937Lithium hydroxide, monohydrateHCID 12944632L-valyl L-valine methyl esterHCID 56988104Methyl (2-oxo-3-benzyl-5-methyl-cyclohept-4-en-1-yl)-ethanoateHCID 178418300HCID 178418300, compound

Product 1

HCID 700844262-(2-Oxo-3-benzyl-5-methyl-cyclohept-4-en-1-yl)-1-oxo-ethyl-valinyl valine methyl ester

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolventHCID 312751,4-DioxaneSolvent

Procedure

To the above keto ester (23) (0.51 g) in 4:1 dioxane, water (10 mL) was added LiOH.H2O (82 mg). The reaction was stirred overnight at room temperature, evaporated, taken up in ethyl acetate washed with aqueous 1N HCl, saturated NaCl, dried over MgSO4 and evaporated to give the crude keto acid. The acid was dissolved in DMF (10 mL) to which was added HCl.Val-Val-OMe (0.51 g), triethylamine (1.5 mL), hydroxybenzotriazole (0.48 g) followed by Bop reagent (1.57 g). The reaction was stirred overnight at room temperature and evaporated to dryness. The product (24) was obtained as a mixture of diastereomers by flash chromatography on silica gel eluted with 50% ethyl acetate in n-hexane. (0.44 g, 51%) (24); TLC Rf 0.24 and 0.26 (40% ethyl acetate, n-hexane); 1H NMR (CDCl3) δ0.8-1.0(12H, m) Val γ(CH3)2's, 1.7(3H, s) allylic CH3, 3.7(3H, s) CO2CH3, 3.8 (1H, br s) allylic CH, 4.55 (2H, dd), 5.15 (1H, m) vinylic CH, 7.25 (5H, s) phenyl.

Workup

  1. customevaporated
  2. washwashed with aqueous 1N HCl, saturated NaCl
  3. dry with materialdried over MgSO4
  4. customevaporated
  5. customto give the crude keto acid
  6. stirringThe reaction was stirred overnight at room temperature
  7. customevaporated to dryness

Sources & evidence

ORD record
ord-068582c0f592429ab8c9c11435eafdf8
Source dataset
uspto-grants-1995_08
Patent number
US05438118

Reaction notes

Loading…