PBr3-DMF

Aminothiocarbonylphenyl)methoxy] derivative 384 was obtained from 8-[(4-cyanophenyl)methoxy]-2-cyclohexy 1-2,3,4,6,11,11 a-hexahydro-l/7-pyrazino[l,2-i]isoquinoline-l,4-dione by treatment with (EtO)2P(S)SH and one drop of H2O at room temperature for 17 h, then followed by addition of more H2O (98MIP7). Reaction of 8-[(4-aminothiocarbonylphe-nyl)methoxy] derivative 384 and MeCOCH2Cl yielded 8- [4-(4-methylthia-zol-2-yl)phenyl]methoxy derivative 385. 7-Bromomethyl derivative was prepared from the 8-hydroxymethyl-8-[(4-cyanophenyl)methoxy]-2-cyclo-pentyl-2,3,4,6,11,1 la-hexahydro-177-pyrazino[l, 2-i]isoquinoline-1,4-dione with PBr3 in CH2CI2 at room temperature. 7-[(l-Pyrazolyl)methyl] derivative was obtained from 7-bromomethyl derivative by treatment with pyrazole in the presence of NaH in DMF at 50 °C. 

In the second route98 to thienothiophene (131) [Eq. (41)], 3-thiophene-aldehyde ethyleneacetal (136) was converted into thiophene-2,3-dialdehyde (138), which was reduced to 2,3-bishydroxymethyl-thiophene (139). 139 was converted by PBr3 into 2,3-bisbromomethyl-thiophene (140), which with anhydrous sodium sulfide in DMF formed thienothiophene (131) (27%). 

Scheme 12.25 Targeted functionalization at carbon C6 formation of N,0-acetals and bicyclic lactams. Reagents and conditions (a) Br2 (3.0 equiv), PBr3 (1.2 equiv), HOAc, rt (b) NaN3 (excess), Nal (1 equiv), DMF, 115 °C (c) sec. amine (10 equiv), CH2CI2, rt, 10 h (d) sec. amine (10 equiv), CH2CI2, rt, 72 h (e) KOH, H20, Bu4NI, 40°C.

---