Triethylamine → Ammonium Hydroxide

HRID 1086449Notes

Reaction equation

[Br:1][C:2]1[C:3]2[C:8]([C:9]3[CH:10]=[CH:11][C:12]([S:16]([Cl:19])(=[O:18])=[O:17])=[CH:13][C:14]=3[CH:15]=1)=[CH:7][CH:6]=[CH:5][CH:4]=2.[NH:20]1[CH2:26][CH2:25][CH2:24][NH:23][CH2:22][CH2:21]1.C(N(CC)CC)C>C(Cl)Cl>[OH-:17].[NH4+:20].[ClH:19].[Br:1][C:2]1[C:3]2[C:8]([C:9]3[CH:10]=[CH:11][C:12]([S:16]([N:20]4[CH2:26][CH2:25][CH2:24][NH:23][CH2:22][CH2:21]4)(=[O:18])=[O:17])=[CH:13][C:14]=3[CH:15]=1)=[CH:7][CH:6]=[CH:5][CH:4]=2

Participants

Conditions

Temperature: 0 °C

Procedure

Add the product of step 2 (2.35 g) in methylene chloride (70 mL) dropwise to hexahydro-2H-1,4-diazepine (0.66 g, 6.6 mmol), triethylamine (1.38 mL, 9.9 mmol) in methylene chloride (35 mL) cooled to 0° C. over 10 minutes. Warm the reaction to room temperature for 30 minutes. Concentrate in vacuo to a yellow solid. Chromatograph the solid on a column of silica gel (500 g) eluting with 4:1:95 methanol:ammonium hydroxide:methylene chloride (2 L) to give the title compound, a free base (1.75 g) as a 6.5:1 mixture of isomers. Rf=0.52 5:95 methanol:methylene chloride containing 0.2% ammonium hydroxide). Dissolve the mixture of isomers in aqueous hydrochloric acid (5 mL, 1N) and concentrate to a white solid. Separate the isomers (100 mg) on a high pressure reversed-phase silica gel column (C18 Dynamax Semiprep 60A®, trademark of Rainin Instruments, Woburn, Mass. 01801) eluting with a 35:65 mixture of water:methanol buffered with 0.2% trifluoroacetic acid at a flow rate of 10 mL/minute to give 65 mg of the title compound.

Workup

temperatureWarm
customthe reaction to room temperature for 30 minutes
concentrationConcentrate in vacuo to a yellow solid
washeluting with 4:1:95 methanol

Sources & evidence

ORD record: ord-60cf7b1270b949d1916660f1a5f01aab
Source dataset: uspto-grants-1991_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05030631

Reaction notes

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