참여 물질
| 역할 | 이름 | HCID | 투입량 |
|---|
| 반응물 | Phosphoric Acid | HCID 1004 | — |
| 반응물 | Tazarotene | HCID 5381 | — |
| 반응물 | Thiophenol | HCID 7969 | — |
| 반응물 | Sodium Hydroxide | HCID 14798 | — |
| 반응물 | Phosphorus oxide (P4O10) | HCID 14812 | — |
| 반응물 | 2-Butene, 1-bromo-3-methyl- | HCID 70092 | — |
| 반응물 | 6-Ethynyl-4,4-dimethylthiochroman | HCID 10932539 | — |
| 용매 | Acetone | HCID 180 | — |
| 용매 | Benzene | HCID 241 | — |
| 용매 | Phenyl-3-methylbut-2-enylsulfide | HCID 54518102 | — |
| 생성물 | 4,4-Dimethylthiochroman | HCID 11019430 | — |
반응 단계
A key intermediate in the preparation of tazarotene, 4,4-dimethyl-6-ethynylthiochroman (II), is prepared as shown in Scheme I: Thiophenol (1) and 1-bromo-3-methyl-2-butene (2) are heated at reflux with sodium hydroxide in acetone resulting in phenyl-3-methylbut-2-enylsulfide (3). The phenyl-3-methylbut-2-enyl sulfide (3) is cyclized by refluxing with phosphorus pentoxide and phosphoric acid in benzene to yield 4,4-dimethylthiochroman (4). The 4,4-dimethylthiochroman (4) is reacted with acetyl chloride catalyzed by tin (IV) chloride (SnCl4) in benzene resulting in 4,4-dimethyl-6-acetylthiochroman (5). The 4,4-dimethyl-6-acetylthiochroman (5) is dehydrated with lithium diisopropylamide (LDA) and diethyl chlorophosphate in tetrahydrofuran (THF) results in the initial 6-ethenyl phosphonate intermediate (6). This intermediate undergoes further reaction with two equivalents of LDA to give 4,4-dimethyl-6-ethynylthiochroman (II).
출처 및 근거
| DOI | 10.6084/m9.figshare.5104873.v1 |
|---|
| 특허 번호 | US06963002B2 |
|---|
| 출처 데이터셋 | uspto-grants-2005_11 |
|---|
| ORD ID | ord-de2de235b37547c1a2e0ea75bee7cea6 |
|---|
| 출처 메모 | uspto-grants-2005_11 |
|---|
