Ninhydrin → tert-Butyl (3S)-3-aminoazepane-1-carboxylate

温度

-78 °C

(S)-Azepan-3-ylamine (5 g; 43.8 mmol) was dissolved in 100 mL of anhydrous CH2Cl2 and cooled to −78° C. while stirring with a magnetic stirring bar. In another flask N-(tert-butoxycarbonyloxy)succinimide [Boc-OSu] (9.7 g; 45 mmol) was dissolved in 50 mL of anhydrous CH2Cl2. To the stirred solution of the amine was added the solution of the succinimide over a period of 10-15 minutes so as to keep the reaction mixture at −78° C. while stirring. After the addition was complete, the reaction was allowed to warm to room temperature and then stirred for an additional 4 h or until the reaction was complete by TLC (Ninhydrin; Rf 0.3; 0.1:1:10 NH4OH, MeOH; CH2Cl2). The reaction mixture was washed with 50 mL of H2O. The aqueous layer was brought to a pH >13 by the addition of 6N NaOH and extracted with CH2Cl2 (3×100 mL). The organic layer was dried over Na2CO3, filtered, and concentracted in a vacuum to yield pure (S)-3-amino-azepane-1-carboxylic acid tert-butyl ester as a viscous oil (5.1 g, 54%). 1H NMR (d6-DMSO, d 3.4, m, 2H; d 2.89, m, 1H; d 2.71, m, 1H; d 2.54, m, 1H; d 1.54, m, 3H; d 1.34, m, 3H; d 1.27, s, 9H; d 1.12, m, 2H), LC/MS (APCI, ES, M+H=215).

1. customat −78° C.
2. stirringwhile stirring
3. additionAfter the addition
4. temperatureto warm to room temperature
5. stirringstirred for an additional 4 h or until the reaction
6. washThe reaction mixture was washed with 50 mL of H2O
7. additionThe aqueous layer was brought to a pH >13 by the addition of 6N NaOH
8. extractionextracted with CH2Cl2 (3×100 mL)
9. dry with materialThe organic layer was dried over Na2CO3
10. filtrationfiltered

ORDレコード

ord-50b0b9b7170842f397e652c057ae87f0

出典データセット

uspto-grants-2008_09

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07423061B2