Trimethylsilyldiazomethane → 1-tert-butyl 2-methyl (2S,4R)-4-[(7-bromo-6-methoxyisoquinolin-1-yl)oxy]pyrrolidine-1,2-dicarboxylate

HRID 1879274Notes

Reaction equation

HRID 1879274 reaction equation
[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][N:8]=[C:9]2[O:12][C@H:13]2[CH2:17][N:16]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[C@H:15]([C:25]([OH:27])=[O:26])[CH2:14]2)=[CH:4][C:3]=1[O:28][CH3:29].[Si](C=[N+]=[N-])(C)(C)[CH3:31]>CO>[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][N:8]=[C:9]2[O:12][C@H:13]2[CH2:17][N:16]([C:18]([O:20][C:21]([CH3:23])([CH3:24])[CH3:22])=[O:19])[C@H:15]([C:25]([O:27][CH3:31])=[O:26])[CH2:14]2)=[CH:4][C:3]=1[O:28][CH3:29]

Participants

4

Reactant 2

HCID 167693TrimethylsilyldiazomethaneHCID 58005163(4R)-4-[(7-bromo-6-methoxyisoquinolin-1-yl)oxy]-1-(tert-butoxycarbonyl)-L-proline

Product 1

HCID 866371121-tert-butyl 2-methyl (2S,4R)-4-[(7-bromo-6-methoxyisoquinolin-1-yl)oxy]pyrrolidine-1,2-dicarboxylateYield 79%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of compound 122 in MeOH (0.1 M) was added TMS-diazomethane (4.2 eq.) and the mixture was stirred at RT for 20 min. Volatiles were evaporated and the crude purified by chromatography to obtain 1-tert-butyl 2-methyl (2S,4R)-4-[(7-bromo-6-methoxyisoquinolin-1-yl)oxy]pyrrolidine-1,2-dicarboxylate as a pale orange foam (79%). To the previous compound dissolved in toluene (0.1 M) tetrakis-(triphenylphospin)-palladium(0) (0.1 eq.) and vinyltri-N-butyltin (1 eq) were added and the mixture was heated at 100° C. for 20 h. Volatiles were evaporated and the residue purified by chromatography to obtain 1-tert-butyl 2-methyl (2S,4R)-4-[(6-methoxy-7-vinylisoquinolin-1-yl)oxy]pyrrolidine-1,2-dicarboxylate as a pale yellow foam (45%) that was treated with HCl 4N in dioxane (26 eq) at RT. After 30 min volatiles were evaporated to obtain the title compound 123 in quantitative yield. MS (ES+) m/z 329 (M+H)+.

Workup

  1. customVolatiles were evaporated
  2. customthe crude purified by chromatography

Sources & evidence

ORD record
ord-68ea369b0d04406da0d5d08803629714
Source dataset
uspto-grants-2012_11
Patent number
US08314062B2

Reaction notes

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