3,4-Dichlorobenzoic acid → tert-Butyl[(2S)-4-(3,4-dichlorobenzoyl)morpholin-2-yl]methylcarbamate
Reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[Cl:11])[C:5]([OH:7])=O.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.C(N(CC)C(C)C)(C)C.[NH:43]1[CH2:48][CH2:47][O:46][C@@H:45]([CH2:49][NH:50][C:51](=[O:57])[O:52][C:53]([CH3:56])([CH3:55])[CH3:54])[CH2:44]1>CN(C)C=O>[C:53]([O:52][C:51](=[O:57])[NH:50][CH2:49][C@@H:45]1[O:46][CH2:47][CH2:48][N:43]([C:5](=[O:7])[C:4]2[CH:8]=[CH:9][C:10]([Cl:11])=[C:2]([Cl:1])[CH:3]=2)[CH2:44]1)([CH3:56])([CH3:54])[CH3:55]Participants
Reactant 5
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 20 °C
Procedure
A mixture of 3,4-dichlorobenzoic acid (0.5 g), 1-hydroxybenzotriazole (0.376 g), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.432 g), and N,N-diisopropylethylamine (0.485 ml) in N,N-dimethylformamide (10 ml) was stirred at 20° C. for 10 min. The mixture was treated with tert-butyl(2R)-morpholin-2-ylmethylcarbamate (0.500 g, known compound WO 9639407A1) and stirred at 20° C. for 24 h. The mixture was partitioned between ethyl acetate (75 ml) and 2N aqueous hydrochloric acid (50 ml). The phases were separated and the organic extract washed with 2N aqueous hydrochloric acid (50 ml), saturated aqueous sodium hydrogen carbonate (2×50 ml), dried (MgSO4) and filtered. The solvent was removed in vacuo to give the title compound as a yellow oil, (0.774 g).
Workup
- stirringstirred at 20° C. for 24 h
- customThe mixture was partitioned between ethyl acetate (75 ml) and 2N aqueous hydrochloric acid (50 ml)
- customThe phases were separated
- extractionthe organic extract
- washwashed with 2N aqueous hydrochloric acid (50 ml), saturated aqueous sodium hydrogen carbonate (2×50 ml)
- dry with materialdried (MgSO4)
- filtrationfiltered
- customThe solvent was removed in vacuo
Sources & evidence
- ORD record
- ord-ee2163203b874d4c80efef4541125669
- Source dataset
- uspto-grants-2009_07
- Patent number
- US07560548B2
Reaction notes
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