Some tips on 278788-66-2

278788-66-2, (R)-tert-Butyl 3-(hydroxymethyl)piperazine-1-carboxylate is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated

278788-66-2, Into a 5-mL-pressure tube was added 183mg (l.Ommol) of 2,3-difluoro-5- (trifluoromethyl)pyridine, 216mg (l.Ommol) of 1,1-dimethylethyl (3i?)-3-(hydroxymethy I)-I- piperazinecarboxylate, 0.2mL DlEA and 1.OmL DMSO. The mixture was heated at 80 C for overnight. The resulting mixture were filtered and concentrated in vacuo. The residue was purified by using a Gilson preparative HPLC system with a Waters Xterra (C-18) column 100 mm by 50 mm ID, eluting with 20% B to 99% B in 10 min, where A = H2O and B = CH3CN pumped at 150 mL/min to yield 1,1-dimethylethyl (3i?)-4-[3-fluoro-5-(trifluoromethyl)-2-pyridinyl]-3- (hydroxymethyl)- 1 -piperazinecarboxylate as a solid. MS(ESI) 380 [M+H] +.To 20mg (0.053mmol) of 1,1-dimethylethyl (3i?)-4-[3-fluoro-5-(trifluoromethyl)-2- pyridinyl]-3-(hydroxymethyl)-l -piperazinecarboxylate was added 0.5mL DMSO and 20mg of tBuOK in a 5-mL-pressure tube. The mixture was heated at 110 C for overnight. The mixture was filtered and the solution was purified by using a Gilson preparative HPLC system with a Waters Xterra (C- 18) column 100 mm by 50 mm ID, eluting with 20% B to 99% B in 10 min, where A = H2O and B = CH3CN pumped at 150 mL/min to yield 1,1-dimethylethyl (6ai?)-3-(trifluoromethyl)- 6a,7,9,10-tetrahydropyrazino[l,2-rf]pyrido[3,2-][l,4]oxazine-8(6H)-carboxylate as a solid. MS(ESI) 360 [M+H]+.To 40mg of (0.1 lmmol) of 1,1-dimethylethyl (6alphai?)-3-(trifluoromethyl)-6alpha,7,9,10- tetrahydropyrazino[l,2-cr|pyrido[3,2-][l,4]oxazme-8(6H)-carboxylate was added ImL DCM and 0.5mL 50% of TFA in DCE. The mixture was stirred at rt for 6h and concentrated in vacuo (the extra TFA was removed by adding DCE and re-concentrating) to yield crude the TFA salt of (6ocR)- 3-(trifluoromethyl)-6,6alpha,7,8,9,10-hexahydropyrazino[l,2-rf]pyrido[3,2-A][l,4]oxazine. MS(ESI) 260 [M+H]1. The above TFA salt of (6alphai?)-3-(trifluoromethyl)-6,6alpha,7,8,9,10-hexahydropyrazino[l,2- rf]pyrido[3,2-ib][l,4]oxazine were dissolved in 1.OmL DCM and 0.3mL DIEA. Then lOOmg (mmol) of (S)-(+)-Camphotau sulfonylchloride in 0.5mL DCM was slowly added at 0 C. The mixture was stirred at rt for 2h. The resulting solution was concentrated in vacuo. The residue was purified by using a Gilson preparative HPLC system with a Waters Xterra (C- 18) column 100 mm by 50 mm ID, eluting with 20% B to 99% B in 10 min, where A = H2O and B = CH3CN pumped at 150 mL/minto yield (l?,4Z?)-7,7-dimethyl-l-({[(6 alphai?)-3-(trifluoromethyl)-6 alpha,7,9,10- tetrahydropyrazino[ 1 ,2-Patent; SMITHKLINE BEECHAM CORPORATION; WO2007/76318; (2007); A2;,
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