Ethyl Acetate → (2S,5S)-1-tert-butyl 4-methyl 2-((tert-butyldimethylsilyloxy)methyl)-5-hydroxy-5,6-dihydropyridine-1,4(2H)-dicarboxylate

HRID 627141

Reaction equation

HRID 627141 reaction equation
[C:1]([O:5][C:6]([N:8]([C@@H:18]([CH:28]=C)[CH2:19][O:20][Si:21]([C:24]([CH3:27])([CH3:26])[CH3:25])([CH3:23])[CH3:22])[CH2:9][CH:10]([OH:17])[C:11](=C)[C:12]([O:14][CH3:15])=[O:13])=[O:7])([CH3:4])([CH3:3])[CH3:2].C(OCC)(=O)C>C1(C)C=CC=CC=1.CC1C=C(C)C(N2C(=[Ru](Cl)(Cl)=CC3C=CC=CC=3OC(C)C)N(C3C(C)=CC(C)=CC=3C)CC2)=C(C)C=1>[Si:21]([O:20][CH2:19][C@@H:18]1[CH:28]=[C:11]([C:12]([O:14][CH3:15])=[O:13])[C@H:10]([OH:17])[CH2:9][N:8]1[C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])([C:24]([CH3:26])([CH3:27])[CH3:25])([CH3:22])[CH3:23]

Participants

5

Reactant 2

HCID 8857Ethyl Acetate2×HCID 89851332methyl 4-(tert-butoxycarbonyl((S)-1-(tert-butyldimethylsilyloxy)but-3-en-2-yl)amino)-3-hydroxy-2-methylenebutanoate2×

Product 1

HCID 89852366(2S,5S)-1-tert-butyl 4-methyl 2-((tert-butyldimethylsilyloxy)methyl)-5-hydroxy-5,6-dihydropyridine-1,4(2H)-dicarboxylate

Reagents, catalysts & solvents 2

HCID 11763533(1,3-Bis(2,4,6-trimethylphenyl)imidazolidin-2-ylidene)(dichloro)((2-((propan-2-yl)oxy)phenyl)methylidene)rutheniumCatalystHCID 1140TolueneSolvent

Procedure

A stirred solution of methyl 4-(tert-butoxycarbonyl((S)-1-(tert-butyldimethylsilyloxy)but-3-en-2-yl)amino)-3-hydroxy-2-methylenebutanoate (Intermediate 100, 16 g, 37 mmol) in toluene (about 300 mL), at ambient temperature in a heat-dried flask, was thoroughly degassed with argon and placed under a nitrogen atmosphere. To this was added Hoveyda-Grubbs Catalyst 2nd Generation (460 mg, 0.74 mmol). Analysis of the mixture 3.5 hours later by LCMS and TLC (15% ethyl acetate in hexanes) indicated very high conversion of starting material to two major products. The reaction mixture was concentrated in vacuo in the presence of enough silica gel to give a free-flowing powder upon reaching dryness. Normal-phase chromatography (0-100% ethyl acetate in hexanes, 330-g column, 45 minutes) was used to isolate the two compounds; the diastereomer shown above (6.4 g, 43%, dark oil) eluted first.

Workup

  1. customAnalysis of the mixture 3.5 hours
  2. concentrationThe reaction mixture was concentrated in vacuo in the presence of enough silica gel
  3. customto give a free-flowing powder
  4. customto isolate the two compounds
  5. washeluted first

Sources & evidence

ORD record
ord-9b364beaf4cc40a4948a6847af077977
Source dataset
uspto-grants-2016_04
Patent number
US09309245B2

Linked notes

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