関与物質
| 役割 | 名称 | HCID | 仕込み量 |
|---|
| 反応物 | 2,3-Dihydroxybutanedioic Acid | HCID 875 | — |
| 反応物 | 2'-Hydroxyacetophenone | HCID 8375 | — |
| 反応物 | Chroman-2-carboxamide | HCID 18621312 | — |
| 生成物 | 2,3-Dihydroxybutanedioic Acid | HCID 875 | — |
| 生成物 | 3,4-dihydro-2H-1-benzopyran-2-carboxylic acid | HCID 2723665 | — |
| 生成物 | (2S)-3,4-dihydro-2H-1-benzopyran-2-carboxylic acid | HCID 6933105 | — |
| 生成物 | (R)-chroman-2-carboxylic acid | HCID 6933107 | — |
反応手順
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.
情報源と証拠
| DOI | 10.6084/m9.figshare.5104873.v1 |
|---|
| 特許番号 | US07034051B2 |
|---|
| 出典データセット | uspto-grants-2006_04 |
|---|
| ORD ID | ord-4c0daa836a7649648fa3edc2d5a682ff |
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| 出典メモ | uspto-grants-2006_04 |
|---|
