1,1'-Carbonyldiimidazole → (3-{[(1-{[(Tert-butoxycarbonyl)(methyl)amino]methyl}cyclopropyl)carbonyl]amino}-propyl)(triphenyl)phosphonium bromide

HRID 58346Notes

Reaction equation

HRID 58346 reaction equation
[C:1]([O:5][C:6]([N:8]([CH2:10][C:11]1([C:14]([OH:16])=O)[CH2:13][CH2:12]1)[CH3:9])=[O:7])([CH3:4])([CH3:3])[CH3:2].C1N=CN(C(N2C=NC=C2)=O)C=1.[Br-:29].[Br-].[NH3+:31][CH2:32][CH2:33][CH2:34][P+:35]([C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1)([C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1)[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1>CN(C)C=O.C(Cl)Cl>[Br-:29].[C:1]([O:5][C:6]([N:8]([CH2:10][C:11]1([C:14]([NH:31][CH2:32][CH2:33][CH2:34][P+:35]([C:48]2[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=2)([C:36]2[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=2)[C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)=[O:16])[CH2:12][CH2:13]1)[CH3:9])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 60034817HCID 60034817, compoundHCID 178419277HCID 178419277, compound

Product 1

HCID 89462959(3-{[(1-{[(Tert-butoxycarbonyl)(methyl)amino]methyl}cyclopropyl)carbonyl]amino}-propyl)(triphenyl)phosphonium bromideYield 44.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

1-{[(tert-butoxycarbonyl)(methyl)amino]methyl}cyclopropanecarboxylic acid (680 mg, 3.0 mmol) was dissolved in N,N-dimethylformamide (6.8 mL) and treated with N,N-carbonyldiimidazole (571 mg, 3.52 mmol). The mixture was stirred at room temperature for 30 minutes. To the solution was added (3-ammoniopropyl)(triphenyl)phosphonium dibromide (1.93 g, 4.00 mmol). The mixture was stirred overnight at room temperature and then diluted with methylene chloride and washed with 5% aqueous lithium chloride (3 times), 1N aqueous hydrogen chloride, and saturated sodium bicarbonate. The organic solution was dried over anhydrous sodium sulfate, filtered, and concentrated to give crude title compound. The crude product was purified on a silica gel column eluting with a gradient of 0-20% methanol with methylene chloride to isolate the title compound (810 mg, 40%, 91% pure).

Workup

  1. stirringThe mixture was stirred overnight at room temperature
  2. washwashed with 5% aqueous lithium chloride (3 times), 1N aqueous hydrogen chloride, and saturated sodium bicarbonate
  3. dry with materialThe organic solution was dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto give crude title compound
  7. customThe crude product was purified on a silica gel column
  8. washeluting with a gradient of 0-20% methanol with methylene chloride

Sources & evidence

ORD record
ord-ef6fa86c78904968a31e557adb630308
Source dataset
uspto-grants-2016_09
Patent number
US09434753B2

Reaction notes

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