Triphenylphosphine → Ethyl 2-(2-(((2-(benzyloxy)-4,6-dimethylpyridin-3-yl)methyl)(tert-butoxycarbonyl)amino)ethoxy)-3-bromo-6-methyl-5-((methylsulfonyl)oxy)benzoate

HRID 577556Notes

Reaction equation

HRID 577556 reaction equation
[Br:1][C:2]1[C:3]([OH:19])=[C:4]([C:10]([CH3:18])=[C:11]([O:13][S:14]([CH3:17])(=[O:16])=[O:15])[CH:12]=1)[C:5]([O:7][CH2:8][CH3:9])=[O:6].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH2:39]([O:46][C:47]1[C:52]([CH2:53][N:54]([CH2:62][CH2:63]O)[C:55](=[O:61])[O:56][C:57]([CH3:60])([CH3:59])[CH3:58])=[C:51]([CH3:65])[CH:50]=[C:49]([CH3:66])[N:48]=1)[C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>O1CCCC1.O>[CH2:39]([O:46][C:47]1[C:52]([CH2:53][N:54]([C:55]([O:56][C:57]([CH3:59])([CH3:58])[CH3:60])=[O:61])[CH2:62][CH2:63][O:19][C:3]2[C:2]([Br:1])=[CH:12][C:11]([O:13][S:14]([CH3:17])(=[O:15])=[O:16])=[C:10]([CH3:18])[C:4]=2[C:5]([O:7][CH2:8][CH3:9])=[O:6])=[C:51]([CH3:65])[CH:50]=[C:49]([CH3:66])[N:48]=1)[C:40]1[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=1

Participants

7

Reactant 4

HCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 86723695Tert-butyl ((2-(benzyloxy)-4,6-dimethylpyridin-3-yl)methyl)(2-hydroxyethyl)carbamateHCID 86723782Ethyl 3-bromo-2-hydroxy-6-methyl-5-((methylsulfonyl)oxy)benzoate

Product 1

HCID 86723783Ethyl 2-(2-(((2-(benzyloxy)-4,6-dimethylpyridin-3-yl)methyl)(tert-butoxycarbonyl)amino)ethoxy)-3-bromo-6-methyl-5-((methylsulfonyl)oxy)benzoateYield 53.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of ethyl 3-bromo-2-hydroxy-6-methyl-5-((methylsulfonyl)oxy)benzoate (116d, 593 mg, 1.5 mmol), triphenylphosphine (0.50 g, 1.9 mmol), and tert-butyl ((2-(benzyloxy)-4,6-dimethylpyridin-3-yl)methyl)(2-hydroxyethyl)carbamate (Cpd LL, 0.54 g, 1.5 mmol) in tetrahydrofuran (12 mL) was cooled to 0° C. then diisopropyl azodicarboxylate (0.40 mL, 1.9 mmol) was added drop wise. The reaction was slowly warmed to room temperature and stirred overnight. The reaction was diluted with water (15 mL) and extracted with ethyl acetate (2×15 mL). The combined organic layers were washed with brine (15 mL), dried over magnesium sulfate, concentrated under vacuum, and purified by column chromatography (20% EtOAc/Heptane) to give ethyl 2-(2-(((2-(benzyloxy)-4,6-dimethylpyridin-3-yl)methyl)(tert-butoxycarbonyl)amino)ethoxy)-3-bromo-6-methyl-5-((methylsulfonyl)oxy)benzoate (116e, 0.58 g, 52% yield) as a white solid.

Workup

  1. extractionextracted with ethyl acetate (2×15 mL)
  2. washThe combined organic layers were washed with brine (15 mL)
  3. dry with materialdried over magnesium sulfate
  4. concentrationconcentrated under vacuum
  5. custompurified by column chromatography (20% EtOAc/Heptane)

Sources & evidence

ORD record
ord-2d94c3680ab24c958277d8ccc03aa2ef
Source dataset
uspto-grants-2015_05
Patent number
US09040515B2

Reaction notes

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