Sequential treatment with
trimethylsilyl iodide then methanol can also be used for Boc deprotection,[7][8] especially where other deprotection methods are too harsh for the substrate.[9] The mechanism involves silylation of the carbonyl oxygen and elimination of tert-butyl iodide (1),
methanolysis of the silyl ester to the
carbamic acid (2) and finally
decarboxylation to the amine (3).[10]
Heating a mixture of the amine to be protected and di-tert-butyl dicarbonate in
tetrahydrofuran (THF) at 40 °C[12]
Add the amine to
sodium hydroxide and di-tert-butyl dicarbonate in water and THF at 0 °C then warm to ambient temperature.[13]
Heating a mixture of the amine to be protected and di-tert-butyl dicarbonate in a biphasic mixture of chloroform and aqueous sodium bicarbonate at reflux for 90 minutes.[14]
BOC-protected amines are prepared using the reagent
di-tert-butyl-iminodicarboxylate. Upon deprotonation, this reagent affords a doubly BOC-protected source of NH− 2, which can be N-alkylated. The approach is complementary to the
Gabriel synthesis of amines.
^E. A. Englund; H. N. Gopi; D. H. Appella (2004). "An Efficient Synthesis of a Probe for Protein Function: 2,3-Diaminopropionic Acid with Orthogonal Protecting Groups". Org. Lett.6 (2): 213–215.
doi:
10.1021/ol0361599.
PMID14723531.
^D. M. Shendage; R. Fröhlich; G. Haufe (2004). "Highly Efficient Stereoconservative Amidation and Deamidation of α-Amino Acids". Org. Lett.6 (21): 3675–3678.
doi:
10.1021/ol048771l.
PMID15469321.
^Vommina V. Sureshbabu; Narasimhamurthy Narendra (2011).
"Protection Reactions". In Andrew B. Hughes (ed.). Protection Reactions, Medicinal Chemistry, Combinatorial Synthesis. Amino Acids, Peptides and Proteins in Organic Chemistry. Vol. 4.
Wiley-VCH. pp. XVIII–LXXXIV.
doi:
10.1002/9783527631827.ch1.
ISBN9783527641574.
^Zhijian Liu; Nobuyoshi Yasuda; Michael Simeone; Robert A. Reamer (2014). "N-Boc Deprotection and Isolation Method for Water-Soluble Zwitterionic Compounds". J. Org. Chem.79 (23): 11792–11796.
doi:
10.1021/jo502319z.
PMID25376704.
^Englund, Ethan A.; Gopi, Hosahudya N.; Appella, Daniel H. (2004). "An Efficient Synthesis of a Probe for Protein Function: 2,3-Diaminopropionic Acid with Orthogonal Protecting Groups". Org. Lett.6 (2): 213–215.
doi:
10.1021/ol0361599.
PMID14723531.
^Stahl, Glenn L.; Walter, Roderich; Smith, Clark W. (1978). "General Procedure for the Synthesis of Mono-N-Acylated 1,6-Diaminohexanes". J. Org. Chem.43 (11): 2285–2286.
doi:
10.1021/jo00405a045.
^Prashad, Mahavir; Har, Denis; Hu, Bin; Kim, Hong-Yong; Girgis, Michael J.; Chaudhary, Apurva; Repič, Oljan; Blacklock, Thomas J.; Marterer, Wolfgang (2004). "Process Development of a Large-Scale Synthesis of TKA731: A Tachykinin Receptor Antagonist". Org. Process Res. Dev.8 (3): 330–340.
doi:
10.1021/op0341824.