ω,ω'
2
An Efficient and Economical Method for the Preparation of Fmoc-Arg (Boc) -OH
Experimental
the solid disappeared little by little. The reaction mix-
ture was partitioned by adding 5% KHSO (250 mL).
The organic phase was washed with 5% KHSO (150
mL) many times till the base DIEA was gone, then
washed with water, brine and dried over MgSO
Evaporation of chloroform and drying in vacuo gave
4
Cu(II)-N-Boc-ornithine complex (2) Cu(II) or-
nithine complex was prepared as reported by Kurtz. A
solution of ornithine dihydrochloride (150 g, 0.73 mol)
1
5
4
4
.
3 2 2
and 150 g CuCO Cu(OH) •xH O in water (1000 mL)
was refluxing for 2 h. The solid was removed by filtra-
tion at 60 ℃ to give blue solution. After cooled down to
room temperature, the blue solution was poured into 5 L
ω,ω'
5
6.1 g of Fmoc-Arg (Boc)
with purity greater than 98% and yield 95.0%. H NMR
(DMSO-d , 300 MHz) δ: 1.38 (s, 9H), 1.47 (s, 9H), 1.45
2
-OH as amorphous solid
1
-
1
6
flask, followed with 1 mol•L NaHCO
3
(1000 mL), and
—
1.60 (m, 3H), 1.61—1.72 (m, 1H), 3.35 (b, 2H), 3.93
acetone (2000 mL). the mixture was stirred mechani-
cally and added liquid Boc
—
4.04 (m, 1H), 4.20—4.29 (m, 3H), 7.36—7.49 (m,
2
O (223 g, 1.02 mol), keeping
-
1
4H), 7.84 (d, J=7.2 Hz, 2H), 7.96 (d, J=7.2 Hz, 2H),
pH 10 with the solution of 2 mol•L NaOH. In the
course of 4 h stirring, a blue solid precipitated, the mix-
ture was acidified to pH 4—5 with acetic acid. 1 h later,
the mixture was filtrated and the solid was washed with
water. After dried in vacuo, triturated and washed with
acetone and chloroform consequently, the blue solid
was obtained (117 g, yield 70%).
8
.05 (s, 1H), 8.35 (s, 1H), 11.51 (b, 1H); MS m/z: 597.1
+
(
M+H) .
Conclusion
This work developed a useful and convenient syn-
ω,ω'
2
thesis method for Fmoc-Arg (Boc) OH in perfect
Fmoc-ornithine (Boc) (3) To a solution of Na-
yield. This methodology realized the preparation
cheaply and efficiently under mild conditions, besides;
product isolation is easy in purification.
HCO
3
(33.6 g, 0.4 mol) and EDTA•4Na•2H
2
O (166 g,
0.4 mol) in water (800 mL) was added Cu (N-BocOrn) •
2
2
CuCl (92.1 g, 0.2 mol) in portions, after the blue solid
was all dissolved in that basic water, 800 mL acetone
was added into mixture, the solution of FmocOsu in
acetone was added dropwise into the blue solution till
the compound H-Orn (Boc) disappeared by TLC and
HPLC. The impurity out of the reaction mixture was
extracted with ether acetate/petrol (60 mL/240 mL)
three times and the left aqueous solution was acidified
to pH 2—3 with 3 mol•L HCl solution. The product
was extracted with 300 mL ether acetate twice. The
combined organic phase was washed with water, brine
References
1
Berlinck, R. G. S. Fortschr. Chem. Org. Naturst. 1995, 66,
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2
3
4
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4
and dried over MgSO . After removal of EA by evapo-
ration, the residue was crystallized from EA/PE as white
powder. The product was dried in vacuo to give 168.5 g
1
of product, yield 92.7%. H NMR (DMSO-d
6
, 300 MHz)
δ: 1.28 (s, 9H), 1.35—1.50 (m, 3H), 1.69—1.84 (m, 1H),
2
0
.91 (b, 2H), 3.95 (b, 1H), 4.21—4.36 (m, 3H), 6.78 (b,
.8H), 7.33—7.46 (m, 4H), 7.67 (s, 1H), 7.73 (d, J=7.5
Hz, 2H), 7.90 (d, J=7.5 Hz, 2H), 12.51 (b, 1H); MS
Bernatowicz, M. S.; Wu, Y.; Matsueda, G. R. Tetrahedron
Lett. 1993, 33, 3389.
+
m/z: 455.1 (M+H) (Esi, positive).
ω,ω'
Fmoc-Arg (Boc)
-OH (5) To a solution of
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1700.
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1997, 62, 1540.
2
Fmoc-orn(Boc) (45.4 g, 0.1 mol) in chloroform, the gas
of HCl went through. About 10 min later, white crystals
were collected. The solvent of the reaction was removed
by filtration after the compound Fmoc-orn (Boc) disap-
peared. To a solution of DIEA (38.7 g, 0.3 mol) in
chloroform (200 mL), Fmoc-Orn•HCl was added, and
stirred for 3 min. N,N'-Di-protected-N''-triflyl-
guanidine (38.7 g, 0.099 mol) was dissolved in
1,4-dioxane (200 mL) and added in the stirred suspen-
15 Kurtz, A. C. J. Biol. Chem. 11949, 180, 1253.
sion. In the course of 6 h stirring at room temperature,
(E1003022 Lu, Y.)
Chin. J. Chem. 2010, 28, 1508— 1509
© 2010 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
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