Triethylamine → HCID 178450735, compound

HRID 1948861Notes

Reaction equation

HRID 1948861 reaction equation
[NH2:1][C:2]1[CH:14]=[CH:13][C:5]([C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7])=[CH:4][CH:3]=1.[CH2:15]([O:22][C:23]([NH:25][C:26](=[N:29][C:30]([O:32][CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)=[O:31])SC)=[O:24])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.CCN(CC)CC>C(Cl)Cl>[CH2:15]([O:22][C:23]([N:25]=[C:26]([NH:29][C:30]([O:32][CH2:33][C:34]1[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=1)=[O:31])[NH:1][C:2]1[CH:14]=[CH:13][C:5]([C:6]([O:8][C:9]([CH3:10])([CH3:11])[CH3:12])=[O:7])=[CH:4][CH:3]=1)=[O:24])[C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 233272Benzoic acid, 4-amino-, 1,1-dimethylethyl esterHCID 46642131,3-Bis(benzyloxycarbonyl)-2-methylisothiourea

Product 1

HCID 178450735HCID 178450735, compoundYield 75.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of t-butyl 4-aminobenzoate (2.0 g, 10.3 mmol) in CH2Cl2 (20 mL) was added 1,3-bis(benzyloxycarbonyl)-2-methyl-2-thiopseudourea (5.6 g, 15.5 mmol), Et3N (5.0 mL, 36 mmol), and mercuric chloride (3.37 g, 12.4 mmol). The reaction mixture was stirred overnight at room temperature. The reaction mixture was filtered through Celite®, and the filtrates were concentrated in vacuo and purified by column chromatography (1:1 CH2Cl2/hexanes to 100% CH2Cl2, and then 10% EtOAc/CH2Cl2) to provide tert-butyl 4-(2,3-bis(benzyloxycarbonyl)guanidino)benzoate (3.9 g, 75%). To a pressure bottle was charged 20% palladium hydroxide on carbon (2 g) followed by a solution of t-butyl 4-(2,3bis(benzyloxycarbonyl)guanidine)benzoate (3.9 g, 7.7 mmol) in EtOAc (80 mL). The mixture was stirred under hydrogen at 50 psi at room temperature overnight. The solution was filtered through Celite® and the filtrate evaporated in vacuo to provide t-butyl guanidinobenzoate (1.8 g, 100%). To the guanidine (855 mg, 3.6 mmol) in EtOAc (50 mL) was add 2M HCl in Et2O (1.9 mL, 3.8 mM). The solution was concentrated and the precipitate was collected by filtration, washed with Et2O and dried in vacuo to yield (840 mg, 85%) of the HCl salt.

Workup

  1. filtrationThe reaction mixture was filtered through Celite®
  2. concentrationthe filtrates were concentrated in vacuo
  3. custompurified by column chromatography (1:1 CH2Cl2/hexanes to 100% CH2Cl2

Sources & evidence

ORD record
ord-926db2df84cb47f3b30c87ff8ece89f4
Source dataset
uspto-grants-2013_03
Patent number
US08399659B2

Reaction notes

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