Improved synthesis of the valuable peptidomimetic intermediate 3-azido-4-hydroxy cyclopentanoic acid

Article abstract of DOI:10.1016/j.tetasy.2006.07.001

An improved synthesis of 3-azido-4-hydroxy cyclopentanoic acid 2 is presented. This molecule is useful as a synthetic scaffold for β-turn mimetics on solid phase, with the selectivity of the turns being dependent on the diastereomer employed. A high diast

Full text of DOI:10.1016/j.tetasy.2006.07.001

Tetrahedron: Asymmetry 17 (2006) 2235–2239
Improved synthesis of the valuable peptidomimetic intermediate
3-azido-4-hydroxy cyclopentanoic acid
Emiliano Tamanini,a Michael Watkinsona and Matthew H. Toddb,*
aSchool of Biological and Chemical Sciences, Queen Mary, University of London, Mile End Road, London E1 4NS, UK
bSchool of Chemistry, University of Sydney, NSW 2006, Australia
Received 22 June 2006; accepted 4 July 2006
Available online 27 July 2006
Abstract—An improved synthesis of 3-azido-4-hydroxy cyclopentanoic acid 2 is presented. This molecule is useful as a synthetic scaffold
for b-turn mimetics on solid phase, with the selectivity of the turns being dependent on the diastereomer employed. A high diastereo-
selectivity in the synthesis of this molecule in solution is reported, which may then be attached to the solid phase for the synthesis of
peptidomimetic libraries.
ꢀ 2006 Elsevier Ltd. All rights reserved.
1. Introduction
NH2
HN
Mimics of b-turns are important targets in medicinal
NH
chemistry.1–3 The RGD turn associated with cell adhesion
O
H
N
O
remains one of the most important motifs, with relevance
to the prevention of metastasis and angiogenesis.4 While
the precise nature of the binding between an RGD turn
and its integrin protein target in vivo remains unclear,5 a
critical requirement for effective peptide mimicry is the
three-dimensional arrangement of the amino acid residues
in the turn, which in general terms is highly dependent
on the type of scaffold used as the basis for the mimic.6
NH
N3
O
HN
O
O
HO
OH
HO
NH
O
O
N
H
O
CO2H
We recently pursued the synthesis of an RGD mimic 1
reported by Jacobsen.7 The amino acids are here built onto
a core a-amino alcohol derived from an asymmetric epox-
ide ring opening with an azide.8 The binding selectivity of
the resultant mimics for two important integrin types was
highly dependent on the diastereomer of this core unit.
Control of the stereochemistry in similar reactions is also
important in the synthesis of various inhibitors of HIV
reverse transcriptase.8–10
1
2
instead wished to synthesise the core 3-azido-4-hydroxy
cyclopenanoic acid 2 in quantity in solution for attachment
to various solid supports for library synthesis. The retro-
synthetic routes to this molecule are shown (Scheme 1),
and converge on the commercially available cyclopent-3-
enecarboxylic acid. The first asymmetric step in the synthe-
sis is epoxidation of the double bond. The anti-diastereo-
mer is required for the present applications. To the best
of our knowledge, there is no report on the epoxidation
of the unprotected acid 6, while the unprotected alcohol
7 is known to give a product anti:syn ratio of approxi-
mately 60:40.11 Sterically the anti-diastereomer is favoured,
but hydrogen-bonding interactions between the pendant
group and the epoxidation reagent reduce the selectivity.
In the original communication,7 the asymmetric ring open-
ing was performed on the solid phase, where the diastereo-
merically pure epoxide had been previously attached. We
*
Corresponding author. Tel.: +61 2 9351 2180; fax: +61 2 9351 3329;
e-mail: m.todd@chem.usyd.edu.au
0957-4166/$ - see front matter ꢀ 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2006.07.001

2236
E. Tamanini et al. / Tetrahedron: Asymmetry 17 (2006) 2235–2239
silyl-protecting groups give good diastereoselectivities for
X
X
X
the epoxidation. In our hands, the TBDMS-protected alco-
hol gave a 78:22 anti:syn diastereomeric ratio, and even
though we and others9 have been unable to effect their sep-
aration, a report has appeared in which the diastereomeric
alcohols 5 are separable.15 Ultimately we did not want to
proceed via the alcohol series, mainly because the eventual
ring-opened product 3 of the sequence would require oxi-
dation of the primary alcohol to give a carboxylic acid in
the presence of a secondary alcohol (i.e., 3 to 2), and we
have been unsuccessful in identifying suitable conditions
for this transformation. The epoxidation of protected
cyclopent-3-ene carboxylic esters has been less well studied.
Jacobsen found that the ethyl ester gave a 75:25 anti:syn
ratio with m-CPBA;8 higher selectivities of 92:8 were possi-
ble with molybdenum-catalysed epoxidation with hydro-
peroxides, but competing decomposition of the products
gave diminished yields. Earlier reports on the methyl
ester gave selectivities of between 75:25 and 87:13 in favour
of the anti-diastereomer depending on the conditions
employed.
N3
OH
HO
HO
HO
O
6
7
, X = O
, X = H,H
2
3
, X = O
, X = H,H
4, X = O
5, X = H,H
Scheme 1. Retrosynthetic analysis of 3-azido-4-hydroxy cyclopentanoic
acid.
Several protecting groups have been previously
employed on 6 and 7 to increase the anti:syn ratio (Scheme
2).8–10,12–15 For the protected alcohol, it is known that large
RO
RO
O
7
5
R
Ref
anti:syn ratio
7a
7b
7c
Bz
Fmoc
Ph3Si
12;14
12
70:30; 75:25
75:25
2. Results and discussion
12
80:20
7d TBDMS
12;10;15
89:11; 75:25
We have explored two alternative protecting groups for the
carboxylic acid as a means to access diastereomerically
pure 3-azido-4-hydroxy cyclopentanoic acid (Scheme 3).
Benzyl ester 6d gave a reasonable anti:syn selectivity of
78:22 in the epoxidation reaction, while the TBDPS ester
gave a superior 85:15 ratio. These compare favourably with
the best literature values. It is surprising to note that these
large groups give a similar selectivity to the literature
report for the epoxidation of the far less bulky methyl ester.
We found that TBDMS and trityl esters of 6 are too labile
for the purification of the epoxidation reaction products.
O
O
R'O
R'O
O
4
6
Ref
anti:syn ratio
R
13;14;9;13
75:25; 87:13
75:25
6a
6b
Me
Et
8
14
75:25
6c Pinanoyl
The major anti-diastereomer of the epoxide benzyl ester 4d
may be deprotected to give 4 under standard hydrogeno-
lysis conditions (H2, Pd/C, 1 atm) quantitatively. We
Scheme 2. Literature diastereoselectivity for epoxidation of protected
cyclopent-3-ene carboxylic acid and cyclopent-3-enylmethanol.
O
O
O
O
i)
ii)
RO
RO
HO
RO
O
O
syn
anti
6d
6e
4d
4e
, R = Bn
, R = TBDPS
78
85
22
15
6
iii)
O
O
iv)
N3
N3
OTMS
HO
RO
OH
2d
2e
, 95%, 85% e.e.
, 49%, 87% e.e.
2
Scheme 3. Synthesis of 3-azido-4-hydroxy cyclopentanoic acid via benzyl- and TBDPS-protection of the carboxylic acid. Reagents and conditions: (i) for
6d: BnBr, TBAI, NaHCO3, H2O/CH2Cl2, 70%; for 6e: TBDPSCl, DIPEA, DMAP, CH2Cl2, 71%; (ii) m-CPBA, CH2Cl2, 81%; (iii) TMSN3, (1R,2R)-(ꢀ)-
[1,2-cyclohexanediamino-N,N0-bis(3,5-di-tert-butylsalicylidene)]chromium(III) chloride (2–5 mol %), Et2O; (iv) from 2d, NaOH/THF, 82%; from 2e,
TBAF/THF, 70%.

E. Tamanini et al. / Tetrahedron: Asymmetry 17 (2006) 2235–2239
2237
attempted the asymmetric ring-opening reaction on this
3. Conclusion
free acid, with disappointing results. At low catalytic load-
ings (4 mol %) of Jacobsen’s chromium(III) salen catalyst,
the ring-opening reaction was extremely slow and after
40 h, epoxide 4 clearly remained. Extending the reaction
times and increasing catalyst loading (to 8 mol %) also
proved ineffective with complex reaction mixtures being
In conclusion we have described short, new routes to dia-
stereomerically pure 3-azido-4-hydroxy cyclopentanoic
acid 2, which should be of wide use in the preparation of
b-turn mimics on solid phase, and for the synthesis of
nucleoside analogues.
1
formed (as judged by the H NMR of the crude reaction
mixture). We attempted to purify the reaction mixture
by attaching the crude material onto a 2-chlorotrityl
chloride-based resin, reasoning that TFA cleavage would
then yield pure carboxylic acid 2. Unfortunately, this
procedure resulted in a mixture of two materials being
isolated, the target carboxylic acid 2 and a second similar
material which we believe to be chloride 2f. Jacobsen has
previously noted competing chloride incorporation as a
minor contaminant in a high yielding ring-opening reaction
and attributed this to the presence of the chloride anion in
the pre-catalyst.16 Presumably, due to the lower overall
yield observed herein and the much higher catalyst loading
required, the contamination is more significant here.
4. Experimental
4.1. Cyclopent-3-enecarboxylic acid benzyl ester 6d
A solution of 3-cyclopenten-1-carboxylic acid (1 mmol,
112 mg) in saturated NaHCO3 (2 mL) was added to a solu-
tion of benzyl bromide (1.1 equiv, 1.1 mmol, 188 mg) and
tetrabutylammonium iodide (TBAI) (20 mol %, 74 mg) in
DCM (2 mL). The mixture was vigorously stirred at rt
for 16 h, washed with water and the aqueous phase ex-
tracted with DCM (2 · 10 mL). The organic phases were
collected, dried over MgSO4 and concentrated in vacuo.
The crude material was purified by flash column chroma-
tography on silica gel (n-hexane/EtOAc, 9:1) to give 6d
as a colourless liquid (141 mg, 70%). TLC (n-hexane/
O
Cl
EtOAc 9:1), Rf = 0.56; IR (thin film): 1732, 1419 cmꢀ1
;
HO
1H NMR (CDCl3, 400 MHz): d = 7.34 (m, 5H), 5.65 (s,
2H), 5.13 (s, 2H), 3.16 (tt, J = 9.1, 7.3 Hz, 1H), 2.96–2.64
(m, 4H); 13C NMR (CDCl3, 67.5 MHz): d = 175.6, 136.5,
129.1, 128.6, 128.2 (2C), 66.3, 41.6, 36.4. HRMS (ESI)
calcd for [M+NH4]+, (C13H18O2N)+ 220.1332, found
220.1332.
OTMS
2f
Thus asymmetric ring opening with the Cr-salen catalyst
and TMS-azide of the major diastereomers of epoxides
4d and 4e was investigated and found to give good enantio-
meric excesses in both cases. Ring opening of the benzyl-
protected ester 4d proceeded more smoothly, however, giv-
ing 2d in nearly quantitative yield and 85% ee. Removal of
the protecting groups in both cases was facile and 2 was
most conveniently obtained by sodium hydroxide-mediated
cleavage of both benzyl and TMS protecting groups.
4.2. trans-3,4-Epoxycyclopentanecarboxylic acid benzyl
ester anti-4d
To a cooled solution (0 ꢁC) of 6d (1 mmol, 202 mg) in
DCM (10 mL) was added m-CPBA (1.3 equiv, 224 mg) in
three portions. The solution was allowed to warm to room
temperature and stirred at the same temperature for 4 h.
The white precipitate formed was filtered and the solid res-
idue washed with DCM. The organic layer was washed
with saturated NaHCO3 solution and 10% Na2SO4 solu-
tion. The organic phase was dried over MgSO4, filtered
and concentrated in vacuo. The two diastereoisomers were
separated by flash column chromatography on silica gel
(n-hexane/EtOAc, 9:1 to 7:3) to give the anti- and syn-
epoxides as colourless liquids in 81% overall yield and dia-
stereomeric ratio (anti:syn) 78:22.
Attachment of 3-azido-4-hydroxy cyclopentanoic acid
(Scheme 4) to a solid support can be achieved with a
2-chlorotrityl chloride-based resin, 8. The supported azido
alcohol 9 was loaded with an Fmoc-protected amino acid
to give ester 10. The overall yield of the loading steps
(cyclopentanoic acid and amino acid) was found to be ca.
40%, as determined by a combination of Fmoc cleavage
and quantitation, mass gain of the two resin-bound species
and chlorine elemental analysis.
O
O
i)
O
ii)
N3
O
N3
Cl
O
O
OH
NHFmoc
8
9
10
t
CO2 Bu
Scheme 4. Attachment of aspartic acid to solid-supported 3-azido-4-hydroxy cyclopentanoic acid. Reagents and conditions: (i) 2, DIPEA, DCM/DMF;
(ii) Fmoc-Asp(OtBu)–OH, EDC, DMAP, DMF.

2238
E. Tamanini et al. / Tetrahedron: Asymmetry 17 (2006) 2235–2239
4.2.1. anti-4d (major diastereoisomer). TLC (n-hexane/
EtOAc 8:2), Rf = 0.54; IR (thin film) 1732, 1496,
4.5. Cyclopent-3-enecarboxylic acid tert-butyldiphenylsilyl
ester 6e
1454 cmꢀ1 1H NMR (CDCl3, 270 MHz): d = 7.22 (m,
;
5H), 5.02 (s, 2H), 3.34 (s, 2H), 2.60 (app. quin,
J = 8.1 Hz, 1H), 2.22 (dd, J = 13.8 and 8.1 Hz, 2H), 1.77
(dd, J = 13.8 and 9.9 Hz, 2H); 13C NMR (CDCl3,
67.5 MHz): d = 174.5, 136.2, 128.6, 128.2, 128.0, 66.2,
56.0, 37.5, 31.2. HRMS (ESI) calcd for [M+Na]+,
(C13H14O3Na)+ 241.0835, found 241.0832.
TBDPSCl (1.1 mmol, 306 mg) was added to a solution of
3-cyclopenten-1-carboxylic acid (1 mmol, 211 mg), DIPEA
(2 mmol, 258 mg) and DMAP (10 mol %) in DCM
(10 mL), and the mixture stirred overnight at rt. The reac-
tion mixture was washed with brine and the aqueous layer
extracted with DCM (3 · 20 mL). The organic phases were
collected, dried over MgSO4 and concentrated in vacuo.
The crude material was purified by flash-chromatography
on silica gel (n-hexane 100% to n-hexane/EtOAc, 7:3) to
give 6e as a clear liquid (248 mg, 71%). TLC (n-hexane/
EtOAc 8:2), Rf = 0.74; IR (thin film): 1724, 1473,
4.2.2. syn-4d (minor diastereoisomer). TLC (n-hexane/
EtOAc 8:2), Rf = 0.38; IR (thin film) 1732, 1496,
1454 cmꢀ1 1H NMR (CDCl3, 270 MHz): d = 7.33 (m,
;
5H), 5.11 (s, 2H), 3.46 (s, 2H), 2.78–2.69 (m, 3H), 1.85
(dd, J = 14.6 and 9.1 Hz, 2H).
1427 cmꢀ1 1H NMR (CDCl3, 270 MHz): d = 7.66 (m,
;
4H), 7.37 (m, 6H), 5.68 (s, 2H), 3.26 (m, 1H), 2.72 (m,
4H), 1.09 (s, 9H); 13C NMR (CDCl3, 67.5 MHz):
d = 175.1, 135.5, 132.2, 130.3, 129.3, 127.9, 43.6, 36.5,
27.2, 19.4. HRMS (ESI) calcd for [M+Na]+, (C22H26O2Si-
Na)+ 373.1594, found 373.1593.
4.3. (1R,3S,4S)-3-Azido-4-trimethylsilanyloxy-cyclo-
pentane-1-carboxylic acid benzyl ester 2d
To a solution of (1R,2R)-(ꢀ)-[1,2-cyclohexanediamino-
N,N0-bis(3,5-di-tert-butylsalicylidene)]chromium(III) chlo-
ride (0.02 mol, 13 mg) in dry Et2O was added anti-4d
(1 mmol, 218 mg) under N2. After 15 min, TMSN3
(1.1 mmol, 127 mg) was added and the brown solution stir-
red at room temperature for 30 h. The solvent was removed
in vacuo and the residue filtered through a plug of silica gel
with n-hexane/EtOAc (8:2) to provide 2d as a pale yellow
oil (95% yield, 85% ee). The ee was determined by chiral
HPLC (n-hexane/i-PrOH 99.7:0.3 CHIRACEL OD
0.45 · 25 cm, 1 mL/min). Rt = 13.867 min (minor enantio-
mer) and 15.527 min (major enantiomer). The other enan-
tiomer was prepared following the same procedure using
(1S,2S) catalyst (Rt = 13.867 min). Assignment of absolute
stereochemistry is based on the assignments previously
reported.7 TLC (n-hexane/EtOAc 8:2), Rf = 0.79; IR (thin
film) 2106, 1732, 1265 cmꢀ1; 1H NMR (CDCl3, 270 MHz):
d = 7.34 (m, 5H), 5.13 (s, 2H), 4.07 (dd, J = 11.1 and
5.4 Hz, 1H), 3.68 (dd, J = 11.8 and 6.9 Hz, 1H), 3.06
(app. quin, J = 7.4 Hz, 1H), 2.36–2.15 (m, 2H), 1.93–1.82
(m, 2H), 0.13 (s, 9H); 13C NMR (CDCl3, 67.5 MHz):
d = 174.9, 136.0, 128.7, 128.3, 128.2, 76.9, 68.0, 66.7,
39.1, 35.8, 31.8, 0.04. HRMS (ESI) calcd for [M+H]+,
(C16H24N3O3Si)+ 334.1581, found 334.1581.
4.6. anti-3,4-Epoxycyclopentanecarboxylic acid tert-butyl-
diphenylsilyl ester anti-4e
To a cooled solution (0 ꢁC) of 6e (1 mmol, 366 mg) in
DCM (10 mL) was added m-CPBA (1.3 equiv, 224 mg) in
three portions. The solution was allowed to warm to room
temperature and stirred at the same temperature for 4 h.
The white precipitate formed was filtered and the solid res-
idue rinsed with DCM. The organic layer was then washed
with a saturated NaHCO3 solution and 10% Na2SO4 solu-
tion. The organic phase was dried over MgSO4 and concen-
trated. The two diastereoisomers were separated by flash
column chromatography on silica gel (n-hexane/EtOAc
9:1 to 7:3) to give anti- and syn-epoxides as white solids
in 81% overall yield and diastereomeric ratio (anti:syn)
85:15.
4.6.1. anti-4e (major diastereoisomer). TLC (n-hexane/
EtOAc 8:2), Rf = 0.53; Mp: 82–83 ꢁC; IR (thin film)
1716, 1427, 1330 cmꢀ1 1H NMR (CDCl3, 270 MHz):
;
d = 7.64 (m, 4H), 7.39 (m, 6H), 3.52 (s, 2H), 2.83 (m,
1H), 2.42 (dd, J = 14.1 and 7.9 Hz, 2H), 1.92 (dd,
J = 14.1 and 9.9 Hz, 2H), 1.08 (s, 9H); 13C NMR (CDCl3,
67.5 MHz): d = 173.9, 135.4, 131.8, 130.3, 127.9, 56.4, 39.3,
31.3, 27.0, 19.3. HRMS (ESI) calcd for [M+Na]+,
(C22H26O3SiNa)+ 389.1543, found 389.1546.
4.4. (1R,3S,4S)-3-Azido-4-hydroxy-cyclopentane-1-carb-
oxylic acid 2
To a solution of 2d (1 mmol, 333 mg) in THF (10 mL) was
added 1 M NaOH (4 mL). The mixture was stirred at rt for
4 h. THF was evaporated and the aqueous phase extracted
with DCM (three times). The aqueous phase was acidified
with 10% HCl to pH 4 and concentrated. The residue was
taken up with DCM and the precipitate filtered. The solid
was rinsed with DCM, and the organic phase dried over
MgSO4 and concentrated in vacuo to give 2 as a pale
yellow oil (82% yield). IR (thin film) 3700–2400 (broad),
4.6.2. syn-4e (minor diastereoisomer). TLC (n-hexane/
EtOAc 8:2), Rf = 0.40; Mp: 93–95 ꢁC; IR (thin film)
1716, 1427, 1330 cmꢀ1 1H NMR (CDCl3, 270 MHz):
;
d = 7.69 (m, 4H), 7.37 (m, 6H), 3.50 (s, 2H), 2.80 (m,
3H), 1.88 (dd, J = 14.6 and 8.9 Hz, 2H), 1.11 (s, 9H).
4.7. (1R,3S,4S)-3-Azido-4-trimethylsilanyloxy-cyclo-
pentane-1-carboxylic acid tert-butyldiphenylsilyl ester 2e
3348, 2110, 1708, 1419 cmꢀ1
;
1H NMR (CDCl3,
270 MHz): d = 6.50 (br s, 1H), 4.17 (m, 1H), 3.76 (m,
1H), 3.18–2.98 (m, 1H), 2.49–2.10 (m, 2H), 2.10–1.84 (m,
2H); 13C NMR (CDCl3, 67.5 MHz): d = 180.6, 76.6, 67.7,
39.1, 35.2, 32.0. HRMS (ESI) calcd for [M+Na]+,
(C6H9N3O3Na)+ 194.0536, found 194.0535.
To a solution of (1R,2R)-(ꢀ)-[1,2-cyclohexanediamino-
N,N0-bis(3,5-di-tert-butylsalicylidene)]chromium(III) chlo-
ride (0.05 mol, 33 mg) in dry Et2O (5 mL) was added
anti-4e (1 mmol, 366 mg) under N2. After 15 min, TMSN3
(3 mmol, 346 mg) was added and the brown solution stir-

E. Tamanini et al. / Tetrahedron: Asymmetry 17 (2006) 2235–2239
2239
red at rt for 72 h. The solvent was removed in vacuo and
the residue filtered through a plug of silica gel with n-hex-
ane/EtOAc (8:2) to provide 2e as a pale yellow oil (49%
yield, 87% ee). The ee was determined by chiral HPLC
(n-hexane/i-PrOH 99.8:0.2 Chiracel OD 0.45 · 25 cm,
1 mL/min). Rt = 13.837 min (minor enantiomer) and
14.377 min (major enantiomer). The other enantiomer
was prepared following the same procedure using (1S,2S)
catalyst (Rt = 13.837 min). TLC (n-hexane/EtOAc 8:2),
The substitution level was determined spectrophotometri-
cally by Fmoc cleavage: in a volumetric flask, a solution
of piperidine (20%) in DMF (0.5 mL) was added to resin
10 (11.6 mg) and the mixture shaken for 15 min. DMF
was then added to bring the volume to 50 mL. The refer-
ence solution was prepared in the same manner without
the addition of the resin. The blank was used to zero the
UV spectrophotometer. The absorbance of the sample
solution at 301 nm was 0.428255. The substitution level
Rf = 0.73; IR (thin film) 2106, 1724, 1473 cmꢀ1
;
1H
was calculated from the equation:18 (Abs301 nm
·
NMR (CDCl3, 270 MHz): d = 7.67 (m, 4H), 7.40 (m,
6H), 4.07 (m, 1H), 3.70 (m, 1H), 3.14 (m, 1H) 2.40–2.21
(m, 2H), 1.97–1.80 (m, 2H), 1.11 (s, 9H), 0.14 (s, 9H);
13C NMR (CDCl3, 67.5 MHz): d = 174.2, 135.4, 131.8,
130.4, 127.8, 77.8, 68.1, 40.9, 35.8, 32.0, 27.1, 19.4, 0.25.
HRMS (ESI) calcd for [M+Na]+, (C25H35N3O3Si2Na)+
504.2109, found 504.2114.
vol (mL)/7800 · m (g)) and determined to be 0.236 mmol/g.
Acknowledgements
We would like to thank the EPSRC for funding (GR/
T17014/01). We wish to acknowledge the use of the
EPSRC’s Chemical Database Service at Daresbury.19
4.8. (1R,3S,4S)-3-Azido-4-hydroxy-cyclopentane-1-carb-
oxylic acid 2
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The solvent was removed and the crude purified by flash
column chromatography (EtOAc/MeOH, 9:1) to give 2
as a colourless liquid (65 mg, 70%). Spectroscopic data as
above.
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DCM): 3500, 2110, 1732, 1708 cmꢀ1
.
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4.10. Coupling of aspartic acid to solid-supported azido
alcohol 10
A solution of Fmoc–Asp(OtBu)–OH (3 equiv, 0.45 mmol,
189 mg), EDC (3 equiv, 0.45 mmol, 86 mg) and DMAP
(3 equiv, 0.45 mmol, 55 mg) in DMF (5 mL) was added
to a suspension of 9 (150 mg, ca. 0.15 mmol reactive sites)
in DMF (1 mL). The mixture was bubbled in a flow of N2
for 3 h. The resin was then filtered, washed with DMF
(3 · 10 mL) and DCM (3 · 10 mL) and then dried in vacuo
overnight to give 10 as a straw powder (174 mg, 40% by
mass). IR (suspension in DCM): 2106, 1728, 1643,
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1600 cmꢀ1
.