Dimethyl Sulfoxide → (9H-Fluoren-9-yl)methyl decyl(2-oxoethyl)carbamate

Temperature

-40 °C

To a solution of oxalyl chloride (12.24 mL) and methylene chloride (50 mL) at −35 to −45° C. was added DMSO (14.75 g) in methylene chloride (25 mL) over 20 minutes. The reaction mixture was stirred for 10 minutes at −35 to −45° C. A solution of N-Fmoc-2-(n-decylamino)ethanol (20.0 g) in methylene chloride (70 mL) was added over 25 minutes and then stirred 40 minutes at −35 to −45° C. Triethylamine (21.49 g) was then added and the mixture stirred for 30 minutes at −10 to −20° C. The reaction mixture was quenched with water (120 mL) followed by concentrated sulfuric acid (20.0 g) while maintaining the internal temperature at 0–5° C. The organic layer was isolated and washed with 2% sulfuric acid (100 mL) followed by water (2×100 mL). The organic solution was distilled under vacuum at 60° C. to about 100 mL. Heptane (100 mL) was added, the temperature of the oil bath raised to 80° C. and the distillation was continued until the residual volume was 100 mL. More heptane (100 mL) was added and the distillation repeated to a volume of 100 mL. The heating bath was replaced with a cold water bath at 15° C. The bath was cooled slowly to 5° C. over 20 minutes to start the precipitation of the product. The slurry was then cooled to −5 to −10° C. and the slurry was stirred for 2 hours. The solid was then collected on a Buchner funnel and washed with cold (−5° C.) heptane (2×15 mL). The wet solid was dried in vacuo to yield the title aldehyde.

1. stirringstirred 40 minutes at −35 to −45° C
2. stirringthe mixture stirred for 30 minutes at −10 to −20° C
3. customThe reaction mixture was quenched with water (120 mL)
4. temperaturewhile maintaining the internal temperature at 0–5° C
5. customThe organic layer was isolated
6. washwashed with 2% sulfuric acid (100 mL)
7. distillationThe organic solution was distilled under vacuum at 60° C. to about 100 mL
8. additionHeptane (100 mL) was added
9. temperaturethe temperature of the oil bath raised to 80° C.
10. distillationthe distillation
11. additionMore heptane (100 mL) was added
12. distillationthe distillation
13. customThe heating bath was replaced with a cold water bath at 15° C
14. temperatureThe bath was cooled slowly to 5° C. over 20 minutes
15. customthe precipitation of the product
16. temperatureThe slurry was then cooled to −5 to −10° C.
17. stirringthe slurry was stirred for 2 hours
18. customThe solid was then collected on a Buchner funnel
19. washwashed with cold (−5° C.) heptane (2×15 mL)
20. customThe wet solid was dried in vacuo

ORD record

ord-74658f37f17a4069944396a838419796

Source dataset

uspto-grants-2007_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07160984B2