Methyl iodide → Acetate
Reaction equation
[C:1]([CH2:8][N:9]1[C:15]2[CH:16]=[CH:17][C:18]([CH2:20][C:21]3[CH:26]=[CH:25][C:24]([C:27]#[N:28])=[CH:23][CH:22]=3)=[CH:19][C:14]=2[C:13](=[O:29])[N:12]([CH2:30][CH2:31][C:32]([O:34][CH2:35][CH3:36])=[O:33])[CH2:11][C:10]1=[O:37])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[OH-].[Na+].IC.[C:42]([O-:45])(=[O:44])[CH3:43].[NH4+:46]>>[C:1]([CH2:8][N:9]1[C:15]2[CH:16]=[CH:17][C:18]([CH2:20][C:21]3[CH:26]=[CH:25][C:24]([C:27](=[NH:46])[NH2:28])=[CH:23][CH:22]=3)=[CH:19][C:14]=2[C:13](=[O:29])[N:12]([CH2:30][CH2:31][C:32]([O:34][CH2:35][CH3:36])=[O:33])[CH2:11][C:10]1=[O:37])([O:3][C:4]([CH3:5])([CH3:7])[CH3:6])=[O:2].[C:42]([O-:45])(=[O:44])[CH3:43]Participants
Procedure
1-(Carbo-t-butoxymethyl)-4-(2-carboethoxyethyl)-7-[(4-cyanophenyl)methyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione (16.0 g, 31 mmol) was placed in a dry 3-necked flask equipped with an inlet tube for gas dispersion and an outlet tube connected to a trap containing 1:1 2M NaOH/Clorox bleach. The flask was flushed with argon gas and anhydrous pyridine (90 mL) was added followed by the addition of triethylamine (70 mL). The resulting solution was saturated with hydrogen sulfide gas. The inlet and outlet tubes were removed and the reaction mixture was heated at 55° C.-60° C. for 21 hours. The reaction mixture was purged with argon and the volatiles removed in vacuo on a rotary evaporator. The residue was taken up in 5:4 dichloromethane/toluene (450 mL) and this was also removed in vacuo on a rotary evaporator. The treatment with dichloromethane/toluene was repeated once more. The residue was taken up in acetone (300 mL) and iodomethane (5.2 mL, 84 mmol) was added via syringe. The reaction mixture was stirred and heated at 60° C.-65° C. for 5.5 hours. The reaction mixture was cooled and the volatiles removed in vacuo on a rotary evaporator. The residue was taken up in anhydrous methanol (200 mL) under and atmosphere of argon and ammonium acetate (9.25 g, 120 mmol) was added. The reaction mixture was stirred at room temperature under an atmosphere of argon for 21 hours. The volatiles removed in vacuo on a rotary evaporator and the residue was taken up in acetonitrile (200 mL) and filtered through a sintered glass funnel. The reaction vessel was rinsed with additional acetonitrile (100 mL) which was also filtered through the sintered glass funnel. The filtrate was concentrated in vacuo on a rotary evaporator and the residue pumped on under high vacuum to yield 1-(carbo-t-butoxymethyl)-4-(2-carboethoxyethyl)-7-[(4-amidinophenyl)methyl]-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione, acetate (18.2 g, 99% yield)
Workup
- customequipped with an inlet tube for gas dispersion and an outlet tube
- customconnected to a trap
- customThe flask was flushed with argon gas and anhydrous pyridine (90 mL)
- additionwas added
- additionfollowed by the addition of triethylamine (70 mL)
- customThe inlet and outlet tubes were removed
- temperaturethe reaction mixture was heated at 55° C.-60° C. for 21 hours
- customThe reaction mixture was purged with argon
- customthe volatiles removed in vacuo on a rotary evaporator
- customthis was also removed in vacuo on a rotary evaporator
- temperatureheated at 60° C.-65° C. for 5.5 hours
- temperatureThe reaction mixture was cooled
- customthe volatiles removed in vacuo on a rotary evaporator
- additionwas added
- stirringThe reaction mixture was stirred at room temperature under an atmosphere of argon for 21 hours
- customThe volatiles removed in vacuo on a rotary evaporator
- filtrationfiltered through a sintered glass funnel
- washThe reaction vessel was rinsed with additional acetonitrile (100 mL) which
- filtrationwas also filtered through the sintered glass funnel
- concentrationThe filtrate was concentrated in vacuo on a rotary evaporator
Sources & evidence
- ORD record
- ord-22e577966fe04cca8ee399c5738a3c59
- Source dataset
- uspto-grants-2001_01
- Patent number
- US06171578B2
Reaction notes
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