CCOC(C1C=CC(C#C[C:14]2[CH:15]=[CH:16][C:17]3[S:23][CH2:22][CH2:21][C:20]([CH3:25])([CH3:24])[C:18]=3[CH:19]=2)=NC=1)=O.CC1(C)C2C(=CC=C(C#C)C=2)SCC1.C1(S)C=CC=CC=1.BrCC=C(C)C.[OH-].[Na+].O=P12OP3(OP(OP(O3)(O1)=O)(=O)O2)=O.P(=O)(O)(O)O>CC(C)=O.C1(C(SC(C2C=CC=CC=2)C=C(C)C)C=C(C)C)C=CC=CC=1.C1C=CC=CC=1>[CH3:24][C:20]1([CH3:25])[C:18]2[C:17](=[CH:16][CH:15]=[CH:14][CH:19]=2)[S:23][CH2:22][CH2:21]1A 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).
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