2,6-Lutidine → Acetic acid 2-[3-(3-azido-4-methyl-benzoylamino)-5-methanesulfonylamino-4-methoxy-phenyl]-2-methyl-propyl ester

HRID 2109294Notes

Reaction equation

HRID 2109294 reaction equation
C(Cl)(=O)C(Cl)=O.[N:7]([C:10]1[CH:11]=[C:12]([CH:16]=[CH:17][C:18]=1[CH3:19])[C:13]([OH:15])=O)=[N+:8]=[N-:9].[NH2:20][C:21]1[CH:22]=[C:23]([C:34]([CH3:41])([CH3:40])[CH2:35][O:36][C:37](=[O:39])[CH3:38])[CH:24]=[C:25]([NH:29][S:30]([CH3:33])(=[O:32])=[O:31])[C:26]=1[O:27][CH3:28].N1C(C)=CC=CC=1C>C(Cl)Cl.C1COCC1.CN(C=O)C.C1COCC1.C(Cl)Cl>[N:7]([C:10]1[CH:11]=[C:12]([CH:16]=[CH:17][C:18]=1[CH3:19])[C:13]([NH:20][C:21]1[CH:22]=[C:23]([C:34]([CH3:41])([CH3:40])[CH2:35][O:36][C:37](=[O:39])[CH3:38])[CH:24]=[C:25]([NH:29][S:30]([CH3:33])(=[O:32])=[O:31])[C:26]=1[O:27][CH3:28])=[O:15])=[N+:8]=[N-:9]

Participants

9

Reactant 4

HCID 79372,6-LutidineHCID 65578Oxalyl chlorideHCID 179730913-Azido-4-methylbenzoic acidHCID 68886045Acetic acid 2-(3-amino-5-methanesulfonylamino-4-methoxy-phenyl)-2-methyl-propyl ester

Product 1

HCID 58861402Acetic acid 2-[3-(3-azido-4-methyl-benzoylamino)-5-methanesulfonylamino-4-methoxy-phenyl]-2-methyl-propyl esterYield 86.8%

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolventHCID 21919333Tetrahydrofurane dichloromethaneSolvent

Procedure

Oxalyl chloride (0.11 mL, 1.3 mmol) was added to a stirring suspension of 148 mg (0.84 mmol) of 3-azido-4-methyl benzoic acid in 5 mL of 1:1 CH2Cl2/THF followed by 1 drop of 10% DMF in THF. After stirring for 1 h, the now homogeneous mixture was concentrated to provide a dark oil. The acid chloride was dissolved in 5 mL of CH2Cl2 and 185 mg (0.56 mmol) of acetic acid 2-(3-amino-5-methanesulfonylamino-4-methoxy-phenyl)-2-methyl-propyl ester was added along with 0.2 mL (1.7 mmol) of 2,6-lutidine. The mixture was stirred overnight, then was diluted with 10 mL of CH2Cl2, and washed with 1 M NaHSO4 (2×), saturated NaHCO3, and brine. The organic portion was dried with Na2SO4, filtered, and concentrated to provide acetic acid 2-[3-(3-azido-4-methyl-benzoylamino)-5-methanesulfonylamino-4-methoxy-phenyl]-2-methyl-propyl ester (238 mg).

Workup

  1. concentrationthe now homogeneous mixture was concentrated
  2. customto provide a dark oil
  3. stirringThe mixture was stirred overnight
  4. washwashed with 1 M NaHSO4 (2×), saturated NaHCO3, and brine
  5. dry with materialThe organic portion was dried with Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-92ecd282b9b84661aac5c7d7e4066741
Source dataset
uspto-grants-2009_04
Patent number
US07514458B2

Reaction notes

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