3-Bromothiophene → (2,2-difluoro-2-pyridin-2yl-1(S)-thiophen-3-ylethyl)-[3,3-dimethyl-1(S)-(4-methyl-2,6,7-trioxa-bicyclo[2.2.2]oct-1-yl)butyl]amine

温度

-40 °C

To a solution of 3-bromothiophene (597 mg, 6.3 mmol) in dry ether (10 ml) at −70° C. was added nBuLi (1.6 M, 2.5 ml) and the reaction mixture was stirred for 2 h at the same temperature. A solution of (2,2-difluoro-2-pyridin-2-ylethylidene)-[3,3-dimethyl-1(S)-(4-methyl-2,6,7-trioxabicyclo[2.2.2]oct-1-yl)butyl]amine (1.16 g, 3.15 mmol) (prepared as described in Example 9 above) in ether (5 ml) was added and stirring was continued while the reaction mixture was allowed to warm to −40° C. The reaction mixture was quenched with water and the organic layer was separated, washed with brine and dried over MgSO4. The crude product was purified by column chromatographed to give (2,2-difluoro-2-pyridin-2yl-1(S)-thiophen-3-ylethyl)-[3,3-dimethyl-1(S)-(4-methyl-2,6,7-trioxa-bicyclo[2.2.2]oct-1-yl)butyl]amine (350 mg) which was converted to 2(S)-[2,2-difluoro-1(S)-(thiophen-3-yl)-2-pyridin-2-ylethylamino]-4,4-dimethylpentanoic acid as described in Example 9, Step 9 above and then converted to the title compound as described in Example 1, Step 12 above.

1. stirringstirring
2. customThe reaction mixture was quenched with water
3. customthe organic layer was separated
4. washwashed with brine
5. dry with materialdried over MgSO4
6. customThe crude product was purified by column
7. customchromatographed

ORDレコード

ord-894d5c25e2aa4ae3a5dc2857ba15a70b

出典データセット

uspto-grants-2011_09

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08013186B2