Aldoxime → (5R)-(9H-fluoren-9-yl)methyl 5-((benzyloxy)(tert-butoxycarbonyl)amino)-3-(((tert-butyldimethylsilyl)oxy)methyl)-2-carbamoyl-5,6-dihydropyridine-1(2H)-carboxylate

HRID 627184Notes

Reaction equation

HRID 627184 reaction equation
[CH2:1]([O:8][N:9]([C:44]([O:46][C:47]([CH3:50])([CH3:49])[CH3:48])=[O:45])[C@H:10]1[CH2:15][N:14]([C:16]([O:18][CH2:19][CH:20]2[C:32]3[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=3[C:26]3[C:21]2=[CH:22][CH:23]=[CH:24][CH:25]=3)=[O:17])[CH:13]([C:33]#[N:34])[C:12]([CH2:35][O:36][Si:37]([C:40]([CH3:43])([CH3:42])[CH3:41])([CH3:39])[CH3:38])=[CH:11]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(=N[OH:54])C>CO.[Cu](Cl)Cl>[CH2:1]([O:8][N:9]([C:44]([O:46][C:47]([CH3:50])([CH3:49])[CH3:48])=[O:45])[C@H:10]1[CH2:15][N:14]([C:16]([O:18][CH2:19][CH:20]2[C:21]3[CH:22]=[CH:23][CH:24]=[CH:25][C:26]=3[C:27]3[C:32]2=[CH:31][CH:30]=[CH:29][CH:28]=3)=[O:17])[CH:13]([C:33](=[O:54])[NH2:34])[C:12]([CH2:35][O:36][Si:37]([C:40]([CH3:41])([CH3:42])[CH3:43])([CH3:39])[CH3:38])=[CH:11]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 2

HCID 7863AldoximeHCID 89852280(5R)-(9H-fluoren-9-yl)methyl 5-((benzyloxy)(tert-butoxycarbonyl)amino)-3-(((tert-butyldimethylsilyl)oxy)methyl)-2-cyano-5,6-dihydropyridine-1(2H)-carboxylate2×

Product 1

HCID 124012978(5R)-(9H-fluoren-9-yl)methyl 5-((benzyloxy)(tert-butoxycarbonyl)amino)-3-(((tert-butyldimethylsilyl)oxy)methyl)-2-carbamoyl-5,6-dihydropyridine-1(2H)-carboxylateYield 89.1%

Reagents, catalysts & solvents 2

HCID 24014Cupric ChlorideCatalystHCID 887MethanolSolvent

Conditions

Temperature
65 °C

Procedure

A mixture of (5R)-(9H-fluoren-9-yl)methyl 5-((benzyloxy)(tert-butoxycarbonyl)amino)-3-(((tert-butyldimethylsilyl)oxy)methyl)-2-cyano-5,6-dihydropyridine-1(2H)-carboxylate (Intermediate 160, 1.3 g, 1.87 mmol), acetaldehyde oxime (0.569 mL, 9.34 mmol) and newly activated copper(II) chloride on 4 Å MS (187 mg, 0.15 mmol) (used 100 mg CuCl2/mol sieves per 1 mmol substrate) in MeOH (5 mL) was stirred under nitrogen at 65° C. for 6 h. The mixture was filtered and evaporated. The residue was purified on silica gel column (0-60%, EtOAc/hexanes). The two diastereomers were combined together to afford the title compound (1.190 g, 89%) as a pale yellow foamy solid.

Workup

  1. filtrationThe mixture was filtered
  2. customevaporated
  3. customThe residue was purified on silica gel column (0-60%, EtOAc/hexanes)

Sources & evidence

ORD record
ord-3a41abe94e954311928342c85ce12107
Source dataset
uspto-grants-2016_04
Patent number
US09309245B2

Reaction notes

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