Butyl nitrite → HCID 6813148, compound
Reaction equation
CO[CH:3]1[CH2:12][CH2:11][C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4]1=[O:13].C([O:18][N:19]=O)CCC.[O-]CC.[K+]>>[OH:18][N:19]=[C:3]1[CH2:12][CH2:11][C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4]1=[O:13]Participants
4
Procedure
Most of the 5, 6, 7, and/or 8-methoxy-1-tetralones are known. See, e.g., Autrey & Scullard, J. Am. Chem. Soc. 90, 4924 (1968); Thomas and Nathan, J. Am. Chem. Soc. 70, 331 (1948); Thrift, J. Chem. Soc. C., 288 (1967). The appropriate methoxy 1-tetralone (Compound 1) is reacted with n-butylnitrite and potassium ethoxide to yield the 2-hydroxyimino-1-tetralone (Compound 2). The latter is reduced over palladium-barium sulfate to give the 2-amino-1-tetralone (Compound 3). ##STR10## Reduction with sodium borohydride leads to the trans 2-amino-1 tetralol (Compound 4). Treatment of Compound 4 with chloroacetyl chloride or a suitably substituted derivative yields the chloroacetamide (Compound 5). (The size of the heterocyclic ring may be increased by substituting chloropropionyl chloride for chloroacetyl chloride.) ##STR11## Reaction of (Compound 5) with sodium hydride or sodium hydroxide leads to ring closure to the lactam (Compound 6). Reduction of this lactam with lithium aluminum hydride gives the amine (Compound 7) in which A is --CH2 --. ##STR12## Alkylation with RI or RBr yields the tertiary amine (Compound 8). This can also be achieved by acylation of Compound 7 with an alkane carboxylic acid chloride followed by reduction with lithium aluminum hydride. (R5 ' is R5 less one methylene unit.) A third alternative is to directly alkylate Compound 7 with a NaBH4 -carboxylic acid complex. On treatment with boron tribromide the methoxy group (--OCH3) of Compound 8 is converted to a phenol (--OH) to yield Compound 9. (The numbering of the carbons corresponds to A=--CH2 --.) ##STR13##