Triphenylphosphine → tert-butyl (R)-2-[6-bromo-3-bis-(tert-butoxycarbonyl)amino-2-methoxycarbonylphenoxymethyl]pyrrolidine-1-carboxylate

HRID 715947Notes

Reaction equation

HRID 715947 reaction equation
N(C(OC(C)C)=O)=NC(OC(C)C)=O.[Br:15][C:16]1[C:17]([OH:41])=[C:18]([C:23]([N:26]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])=[CH:24][CH:25]=1)[C:19]([O:21][CH3:22])=[O:20].O[CH2:43][C@H:44]1[CH2:48][CH2:47][CH2:46][N:45]1[C:49]([O:51][C:52]([CH3:55])([CH3:54])[CH3:53])=[O:50].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1COCC1>[Br:15][C:16]1[C:17]([O:41][CH2:43][C@H:44]2[CH2:48][CH2:47][CH2:46][N:45]2[C:49]([O:51][C:52]([CH3:53])([CH3:55])[CH3:54])=[O:50])=[C:18]([C:19]([O:21][CH3:22])=[O:20])[C:23]([N:26]([C:27]([O:29][C:30]([CH3:33])([CH3:31])[CH3:32])=[O:28])[C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])=[CH:24][CH:25]=1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 688279N-(tert-Butoxycarbonyl)-D-prolinolHCID 70983234Methyl 3-bromo-6-bis-(tert-butoxycarbonyl)amino-2-hydroxybenzoate2×

Product 1

HCID 71003908tert-butyl (R)-2-[6-bromo-3-bis-(tert-butoxycarbonyl)amino-2-methoxycarbonylphenoxymethyl]pyrrolidine-1-carboxylateYield 100.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Diisopropyl azodicarboxylate (1.21 g) was added to a solution of methyl 3-bromo-6-bis-(tert-butoxycarbonyl)amino-2-hydroxybenzoate (Intermediate 9, 2.23 g), tert-butyl (R)-2-hydroxymethylpyrrolidine-1-carboxylate (1.11 g) and triphenylphosphine (1.57 g) in anhydrous THF (25 mL) and the reaction mixture was stirred at room temperature for 30 minutes, then left to stand overnight. The mixture was concentrated in vacuo and the residue was purified by chromatography on silica, eluting with a mixture of ethyl acetate and cyclohexane with a gradient of 0-30% to give tert-butyl (R)-2-[6-bromo-3-bis-(tert-butoxycarbonyl)amino-2-methoxycarbonyl-phenoxymethyl]pyrrolidine-1-carboxylate (3.17 g) as a colourless gum.

Workup

  1. waitleft
  2. waitto stand overnight
  3. concentrationThe mixture was concentrated in vacuo
  4. customthe residue was purified by chromatography on silica
  5. washeluting with a mixture of ethyl acetate and cyclohexane with a gradient of 0-30%

Sources & evidence

ORD record
ord-555143523e404b76ad08b1e323e910fc
Source dataset
uspto-grants-2015_11
Patent number
US09187494B2

Reaction notes

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