tert-butyl ((2R)-1-((((9H-fluoren-9-yl)methoxy)carbonyl)(2-(((tert-butyldimethylsilyl)oxy)methyl)-1-cyanoallyl)amino)but-3-en-2-yl)(benzyloxy)carbamate → (5R)-(9H-fluoren-9-yl)methyl 5-((benzyloxy)(tert-butoxycarbonyl)amino)-3-(((tert-butyldimethylsilyl)oxy)methyl)-2-cyano-5,6-dihydropyridine-1(2H)-carboxylate

HRID 627183Notes

Reaction equation

HRID 627183 reaction equation
[CH:1]1[C:13]2[CH:12]([CH2:14][O:15][C:16]([N:18]([CH:39]([C:51]#[N:52])[C:40]([CH2:42][O:43][Si:44]([C:47]([CH3:50])([CH3:49])[CH3:48])([CH3:46])[CH3:45])=C)[CH2:19][C@H:20]([N:23]([O:31][CH2:32][C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)[C:24](=[O:30])[O:25][C:26]([CH3:29])([CH3:28])[CH3:27])[CH:21]=C)=[O:17])[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1>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>[CH2:32]([O:31][N:23]([C:24]([O:25][C:26]([CH3:29])([CH3:27])[CH3:28])=[O:30])[C@H:20]1[CH2:19][N:18]([C:16]([O:15][CH2:14][CH:12]2[C:13]3[CH:1]=[CH:2][CH:3]=[CH:4][C:5]=3[C:6]3[C:11]2=[CH:10][CH:9]=[CH:8][CH:7]=3)=[O:17])[CH:39]([C:51]#[N:52])[C:40]([CH2:42][O:43][Si:44]([C:47]([CH3:48])([CH3:49])[CH3:50])([CH3:46])[CH3:45])=[CH:21]1)[C:33]1[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=1

Participants

4

Reactant 1

HCID 131735285tert-butyl ((2R)-1-((((9H-fluoren-9-yl)methoxy)carbonyl)(2-(((tert-butyldimethylsilyl)oxy)methyl)-1-cyanoallyl)amino)but-3-en-2-yl)(benzyloxy)carbamate2×

Product 1

HCID 89852280(5R)-(9H-fluoren-9-yl)methyl 5-((benzyloxy)(tert-butoxycarbonyl)amino)-3-(((tert-butyldimethylsilyl)oxy)methyl)-2-cyano-5,6-dihydropyridine-1(2H)-carboxylateYield 40.7%

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

Conditions

Temperature
90 °C

Procedure

A solution of tert-butyl ((2R)-1-((((9H-fluoren-9-yl)methoxy)carbonyl)(2-(((tert-butyldimethylsilyl)oxy)methyl)-1-cyanoallyl)amino)but-3-en-2-yl)(benzyloxy)carbamate (Intermediate 159, 3.32 g, 4.59 mmol) in toluene (150 mL) was bubbled with nitrogen for 15 minutes. Hoveyda-Grubbs Catalyst 2nd Generation (0.288 g, 0.46 mmol) was added and the mixture was bubbled with nitrogen for an additional 15 minutes. The resulting solution was heated under nitrogen at 90° C. for 2 days. The reaction mixture was evaporated. The residue was purified on silica gel column (0-30% EtOAc/hexane) to afford the title compound (1.300 g, 40.7%) as a light brown film.

Workup

  1. customthe mixture was bubbled with nitrogen for an additional 15 minutes
  2. customThe reaction mixture was evaporated
  3. customThe residue was purified on silica gel column (0-30% EtOAc/hexane)

Sources & evidence

ORD record
ord-68dec6a226e14fa3a45ed2414dbd41d0
Source dataset
uspto-grants-2016_04
Patent number
US09309245B2

Reaction notes

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