Ethyl chloroformate → (S)-N-(3,7-Dimethyl-3,7-diazabicyclo[3.3.1]non-9-yl)-4-amino-5-chloro-2-(1-methyl-2-butynyl)oxybenzamide

HRID 1489046

Reaction equation

HRID 1489046 reaction equation
[NH2:1][C:2]1[C:10]([Cl:11])=[CH:9][C:5]([C:6]([OH:8])=O)=[C:4]([O:12][C@@H:13]([CH3:17])[C:14]#[C:15][CH3:16])[CH:3]=1.ClC(OCC)=O.[NH2:24][CH:25]1[CH:30]2[CH2:31][N:32]([CH3:34])[CH2:33][CH:26]1[CH2:27][N:28]([CH3:35])[CH2:29]2.[OH-].[Na+]>ClCCl.O.C(N(CC)CC)C>[CH3:34][N:32]1[CH2:33][CH:26]2[CH:25]([NH:24][C:6](=[O:8])[C:5]3[CH:9]=[C:10]([Cl:11])[C:2]([NH2:1])=[CH:3][C:4]=3[O:12][C@@H:13]([CH3:17])[C:14]#[C:15][CH3:16])[CH:30]([CH2:29][N:28]([CH3:35])[CH2:27]2)[CH2:31]1

Participants

8

Reactant 4

HCID 10928Ethyl chloroformateHCID 14798Sodium HydroxideHCID 15258856(S)-4-amino-5-chloro-2-[(1-methyl-2-butynyl)oxy]benzoic acidHCID 543841879-Amino-3,7-dimethyl-3,7-diazabicyclo[3.3.1]nonane2×

Product 1

HCID 54072834(S)-N-(3,7-Dimethyl-3,7-diazabicyclo[3.3.1]non-9-yl)-4-amino-5-chloro-2-(1-methyl-2-butynyl)oxybenzamideYield 74.6%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×HCID 8471TriethylamineSolvent

Procedure

A solution of 546 mg of (S)-4-amino-5-chloro-2-[(1-methyl-2-butynyl)oxy]benzoic acid and 0.9 ml of triethylamine in 10 ml of dichloromethane was cooled with ice. followed by the addition thereto of 0.225 ml of ethyl chloroformate. The obtained mixture was stirred for 10 minutes, while the temperature was brought to room temperature. 400 mg of 9-amino-3,7-dimethyl-3,7-diazabicyclo[3.3.1]nonane was added to the resulting mixture at room temperature. The obtained mixture was stirred for 30 minutes, followed by the addition thereto of 200 mg of 9-amino-3,7-dimethyl-3,7-diazabicyclo[3.3.1]nonane at room temperature. The obtained mixture was stirred for one hour, followed by the addition thereto of dichloromethane and water. The pH of the aqueous layer was adjusted to 10 or above with a 2.5N aqueous solution of sodium hydroxide. The organic phase was recovered, dried over anhydrous magnesium sulfate, and concentrated in a vacuum. The residue was purified by silica gel column chromatography (with 0 to 10 to 20% methanol/chloroform and then with chloroform/methanol/aqueous ammonia (75/25/1.5) to give 650 mg of the title compound.

Workup

  1. additionfollowed by the addition
  2. customwas brought to room temperature
  3. stirringThe obtained mixture was stirred for 30 minutes
  4. additionfollowed by the addition
  5. customat room temperature
  6. stirringThe obtained mixture was stirred for one hour
  7. additionfollowed by the addition
  8. customThe organic phase was recovered
  9. dry with materialdried over anhydrous magnesium sulfate
  10. concentrationconcentrated in a vacuum
  11. customThe residue was purified by silica gel column chromatography (with 0 to 10 to 20% methanol/chloroform

Sources & evidence

ORD record
ord-ae195a8e5a56441c8081b957b49a1bcc
Source dataset
uspto-grants-1997_10
Patent number
US05677311

Linked notes

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