(1S,2R)-(-)-1-Amino-2-indanol → (S)-1-(4-Benzyloxy-3-nitrophenyl)-2-bromoethanol

온도

0 °C

A cold (5° C.) solution of (1S,2R)-1-amino-2-indanol (400 mg, 2.68 mmol) in THF (160 mL) was added dropwise to a cold (0° C.) solution of borane-diethylaniline complex (7.0 g, 43 mmol) in THF (20 mL). After complete addition, the resulting solution was stirred at (0° C.) for 30 min then 2-bromo-4′-benzyloxy-3′-nitroacetophenone (20.0 g, 57.1 mmol) was added in three portions over a 30 min period. The resulting solution was stirred at <5° C. for 1 h, quenched by dropwise addition of acetone (17 mL) then allowed to warm to ambient temperature overnight. The reaction mixture was concentrated in vacuo to a residue, which was dissolved in toluene (100 mL) and washed in succession with 10% H2SO4 (2×45 mL), H2O (2×45 mL) and sat. brine (1×40 mL). The organic layer was dried over MgSO4, clarified then concentrated in vacuo to a volume of ˜40 mL. Heptane (45 mL) was slowly added to give a thick slurry. The solid was collected on a filter and washed with heptane (2×5 mL). This material was dissolved in warm toluene (˜50 mL), the solution was clarified then diluted with heptane (50 mL). The resulting mixture was stirred for 30 min, the solids were collected, washed with heptane (2×5 mL) then dried to constant weight in vacuo to give 18.9 g (94.0%) of the title compound.

1. additionAfter complete addition
2. stirringThe resulting solution was stirred at <5° C. for 1 h
3. customquenched by dropwise addition of acetone (17 mL)
4. temperatureto warm to ambient temperature overnight
5. concentrationThe reaction mixture was concentrated in vacuo to a residue, which
6. dissolutionwas dissolved in toluene (100 mL)
7. washwashed in succession with 10% H2SO4 (2×45 mL), H2O (2×45 mL) and sat. brine (1×40 mL)
8. dry with materialThe organic layer was dried over MgSO4
9. concentrationclarified then concentrated in vacuo to a volume of ˜40 mL
10. additionHeptane (45 mL) was slowly added
11. customto give a thick slurry
12. customThe solid was collected on
13. filtrationa filter
14. washwashed with heptane (2×5 mL)
15. dissolutionThis material was dissolved in warm toluene (˜50 mL)
16. additionthe solution was clarified then diluted with heptane (50 mL)
17. stirringThe resulting mixture was stirred for 30 min
18. customthe solids were collected
19. washwashed with heptane (2×5 mL)
20. customthen dried to constant weight in vacuo

ORD 기록

ord-fa43a30a04fc431cb4cead62f6c22181

출처 데이터셋

uspto-grants-2014_03

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08664441B2