Lithium borohydride → (R)-tert-butyl 6-hydroxyhexan-2-ylcarbamate

To a solution of (R)-ethyl 5-(tert-butoxycarbonylamino)hexanoate (1.70 g, 6.56 mmol) in THF (20 mL) was added dropwise a 2.0 M lithium borohydride solution in THF (6.56 mL, 13.1 mmol). After the addition, the reaction mixture was stirred at rt for 20 hr and then 45° C. for 7 hr and again at rt overnight. The reaction mixture was cooled to 0° C. and was quenched carefully with pH 3 buffer solution. Then the resulting white suspension was stirred at rt for 1 hr. The mixture was then partitioned between 1 N aqueous HCl and DCM. The aqueous phase was extracted with DCM (2×). The combined DCM extracts were washed with water (2×), saturated aqueous NaCl, dried over Na2SO4, filtered and concentrated. The obtained oily residue was dried under high vacuum to afford (R)-tert-butyl 6-hydroxyhexan-2-ylcarbamate (1.42 g, 6.53 mmol, 100% yield) as a colorless oil. Anal. Calcd. for C11H23NO3 m/z 217.3. found: 218.1 (M+H)+; 1H NMR (400 MHz, CDCl3) δ ppm 4.34 (s, 2H), 3.64 (d, J=6.3 Hz, 2H), 1.68-1.50 (m, 2H), 1.44 (s, 9H), 1.51-1.32 (m, 5H), 1.12 (d, J=6.6 Hz, 3H).

1. additionAfter the addition
2. wait45° C. for 7 hr
3. customagain at rt
4. customovernight
5. temperatureThe reaction mixture was cooled to 0° C.
6. customwas quenched carefully with pH 3 buffer solution
7. stirringThen the resulting white suspension was stirred at rt for 1 hr
8. customThe mixture was then partitioned between 1 N aqueous HCl and DCM
9. extractionThe aqueous phase was extracted with DCM (2×)
10. washThe combined DCM extracts were washed with water (2×), saturated aqueous NaCl
11. dry with materialdried over Na2SO4
12. filtrationfiltered
13. concentrationconcentrated
14. customThe obtained oily residue was dried under high vacuum

ORD record

ord-a8a4c265d2bf4c609cfe387ea577014b

Source dataset

uspto-grants-2016_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09346852B2