Benzyl Chloride → (S)-2-(benzyloxy)dodecan-1-ol

A 60 wt. % suspension of NaH in mineral oil (2.01 g, 50.3 mmol) was added to an oven-dried round bottom flask containing a magnetic stir bar. THF (120 mL) was added to the flask by syringe under Ar, and the flask was submerged in an ice bath. Crude 402 (14.9 g, 33.5 mmol) was dissolved in anhydrous THF (50 mL) and was added slowly to the stirred suspension of NaH. The reaction mixture was allowed to warm to room temperature. Benzyl chloride (5.8 mL, 50 mmol) was added to the reaction mixture. The flask was fitted with a reflux condenser, and the mixture was warmed to reflux under Ar overnight. After the reaction mixture had cooled, NH4Cl (sat. aq., ˜300 mL) was added slowly to quench residual NaH. The suspension was transferred into a separatory funnel using H2O (300 mL) and Et2O (200 mL). The organic layer was extracted with additional Et2O; ethereal layers were dried over MgSO4, filtered through paper, and concentrated to a yellow oil. This material was purified by chromatography on silica (gradient elution from hexanes to EtOAc); desired fractions were pooled and concentrated affording 15 g of a slightly yellow oil. This oil was dissolved in 1:1 MeOH/THF (100 mL). p-TsOH.H2O (572 mg) was added to the mixture; the solution was stirred for 6 hours. The reaction mixture was concentrated onto Celite by rotary evaporation and purified by chromatography on silica gel (gradient elution from hexanes to ethyl acetate). Fractions containing the desired product were pooled and concentrated affording 403 (5.44 g, 66%) as a clear oil. 1H NMR (400 MHz, CDCl3): δ 7.39-7.29 (m, 5H), 4.64 (d, J=11.6 Hz, 1H), 4.55 (d, J=11.6 Hz, 1H), 3.74-3.67 (m, 1H), 3.60-3.49 (m, 2H), 1.93-1.90 (m, 1H), 1.68-1.60 (m, 1H), 1.53-1.45 (m, 1H), 1.40-1.40 (m, 16H), 0.89 (t, J=6.9 Hz, 3H).

1. additionwas added to an oven-dried round bottom flask
2. additioncontaining a magnetic stir bar
3. customthe flask was submerged in an ice bath
4. customThe flask was fitted with a reflux condenser
5. temperaturethe mixture was warmed
6. temperatureto reflux under Ar overnight
7. temperatureAfter the reaction mixture had cooled
8. customto quench residual NaH
9. customThe suspension was transferred into a separatory funnel
10. extractionThe organic layer was extracted with additional Et2O
11. dry with materialethereal layers were dried over MgSO4
12. filtrationfiltered through paper
13. concentrationconcentrated to a yellow oil
14. customThis material was purified by chromatography on silica (gradient elution from hexanes to EtOAc)
15. concentrationconcentrated
16. customaffording 15 g of a slightly yellow oil
17. concentrationThe reaction mixture was concentrated onto Celite by rotary evaporation
18. custompurified by chromatography on silica gel (gradient elution from hexanes to ethyl acetate)
19. additionFractions containing the desired product
20. concentrationconcentrated

ORD record

ord-cdfce752c1794058850622a2f6c9b9d4

Source dataset

uspto-grants-2015_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08969353B2