Reaction equation
[O:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][CH:2]1[C:11](N)=[O:12].[OH:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[C:21](=O)[CH3:22].[CH:24]([OH:33])([C:30]([OH:32])=[O:31])[CH:25]([OH:29])[C:26]([OH:28])=[O:27]>>[O:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][CH:2]1[C:11]([OH:12])=[O:14].[O:33]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH2:26][CH2:25][C@@H:24]1[C:30]([OH:32])=[O:31].[O:14]1[C:15]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH2:21][CH2:22][C@H:25]1[C:26]([OH:28])=[O:27].[CH:24]([OH:33])([C:30]([OH:32])=[O:31])[CH:25]([OH:29])[C:26]([OH:28])=[O:27]Participants
Reactant 3
Product 4
Procedure
The synthesis of chroman-2-carboxamide derivatives 14, 15, and 16 is summarized in Scheme 7. Chroman-2-carboxylic acid 14a was prepared using known methodology (WO 99/32475) from 2′-hydroxyacetophenone. The racemic acid was coupled with 1-(2-methylamino-(S)-2-phenyl-ethyl)-pyrrolidin-(S)-3-ol using the Mukaiyama acylation conditions described above. The enantiomerically pure (R)-chroman-2-carboxylic acid 14c1 and (S)-chroman-2-carboxylic acid 14c2 were obtained via chiral separation of the racemic acid. The two pure diastereomers 15 and 16, of mixture 14, were respectively prepared by coupling of the enantiomeric pure (R)-chroman-2-carboxylic acid 14c1 or (S)-chroman-2-carboxylic acid 14c2 with 1-(2-methylamino-(S)-2-phenyl-ethyl)-pyrrolidin-(S)-3-ol using TBTU [O-(benzotriazol-1-yl)-N,N,N′, N′-tetramethyluronium tetrafluoroborate] as acylating reagent.
Sources & evidence
- ORD record
- ord-4c0daa836a7649648fa3edc2d5a682ff
- Source dataset
- uspto-grants-2006_04
- Patent number
- US07034051B2
Linked notes
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