Acetic Acid → {1-[Hydroxy-(2-phenyl-[1,3]dithian-2-yl)methyl]pentyl}carbamic acid tert-butyl ester

Temperature

-60 °C

2-Phenyl-1,3-dithiane (Aldrich) (3.79 g; 19.3 mmol) was mixed with dry distilled THF (20 mL) under a nitrogen atmosphere. The solution was cooled to −60° C. and n-buty lithium (1.6M in pentane, 1.56 mmol, 9.74 mL) was added slowly by syringe. The reaction mixture was warmed to −20° C. and held at that temperature for 30 min., and then held at −10° C. for 15 min. The yellow solution was cooled to −78° C. and (1-formylpentyl)carbamic acid tert-butyl ester (1.6 g, 1.4 mmol, in 5 mL THF) was added rapidly (over 20 seconds) and 60 seconds later a mixture of 2 mL acetic acid and 5 mL THF was added rapidly. After warming to 23° C. the solution was concentrated at reduced pressure. Excess 2-phenyl-1,3-dithiane was removed by its crystallization away from the desired product using a minimum of ethyl acetate in hexane. The mother liquors were concentrated and chromatographed using a hexane-ethyl acetate gradient to afford {1-[hydroxy-(2-phenyl-[1,3]dithian-2-yl)methyl]pentyl}carbamic acid tert-butyl ester. (1.7 g, 56% yield).

1. customwith dry
2. distillationdistilled THF (20 mL) under a nitrogen atmosphere
3. temperatureThe reaction mixture was warmed to −20° C.
4. waitheld at −10° C. for 15 min
5. temperatureThe yellow solution was cooled to −78° C.
6. additionwas added rapidly
7. temperatureAfter warming to 23° C. the solution
8. concentrationwas concentrated at reduced pressure
9. customExcess 2-phenyl-1,3-dithiane was removed by its crystallization away from the desired product
10. concentrationThe mother liquors were concentrated
11. customchromatographed

ORD record

ord-b38610035e424a74b6a8b4055fdeb90c

Source dataset

uspto-grants-2010_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07662849B2