Abstract
A practical eight-step synthesis of a key intermediate of beraprost is described. The tricyclic cyclopent[b]benzofuran core can be prepared from 2,6-dibromo-4-chlorophenol. The butyric side chain is introduced by ortho-selective metal–halogen exchange and subsequent coupling with 4-(benzyloxy)butanal. The procedure is operationally simple and amenable to scale-up synthesis.
References
1.
Moncada S.
,
Grygleski S.
,
Bunting S.
and
Vane J.R.
, Nature , 1976 , 263 , 663 .
2.
Johnson R.A.
,
Morton D.R.
,
Kinner J.H.
,
Gorman R.R.
,
McGuire J.C.
,
Sun F.F.
,
Whittaker N.
,
Bunting S.
,
Salmon J.
,
Moncada S.
and
Vane J.R.
, Prostaglandins , 1976 , 12 , 915 .
3.
Johnson R.A.
,
Lincoln F.H.
,
Nidy E.G.
,
Schneider W.P.
,
Thompson J.L.
and
Axen U.
, J. Am. Chem. Soc. , 1978 , 100 , 7690 .
4.
Moncada S.
,
Higgs G.A.
and
Vane J.R.
, Lancet , 1977 , 1 , 18 .
5.
Cho M.J.
and
Allen M.A.
, Prostaglandins , 1978 , 15 , 9453 .
6.
Melian E.B.
and
Goa K.L.
, Drugs , 2002 , 62 , 107 .
7.
Nagase H.
,
Matsumo K.
and
Nishiya H.J.
, Synth. Org. Chem. , 1996 , 54 , 1055 .
8.
Saibal D.
,
Chandrasekhar S.
,
Yadav J.S.
and
Gree R.
, Chem. Rev. , 2007 , 107 , 3286 .
9.
Collins P.W.
and
Djuric S.W.
, Chem. Rev. , 1993 , 93 , 1533
10.
Ohno K.
,
Nagase H.
and
Matsumoto K.
, E.U. Patent: EP0084856A1, issued 20 November 1986 .
11.
Ohno K.
,
Nishiyama H.
,
Nagase H.
,
Matsumoto K.
and
Ishikawa M.
, Tetrahedron Lett ., 1990 , 31 , 4489 .
12.
Wakita H.
,
Matsumoto K.
,
Yoshiwara H.
,
Hosono Y.
,
Hayashi R.
,
Nishiyama H.
and
Nagase H.
, Tetrahedron , 1999 , 55 , 2449 .
13.
Kobayashi Y.
,
Kuramoto R.
and
Takemoto Y.
, Beilstein J. Org. Chem ., 2015 , 11 , 2654 .
14.
Wakita H.
,
Yoshiwara H.
,
Kitano Y.
,
Nishiyama H.
and
Nagase H.
, Tetrahedron: Asymmetry , 2000 , 11 , 2981 .
15.
Yoshida Y.
,
Sato Y.
,
Okamoto S.
and
Sato F.
, J. Chem. Soc., Chem. Commun ., 1995 , 811 .
16.
Larock R.C.
and
Lee N.H.
, J. Org. Chem ., 1991 , 56 , 6253 .
17.
Higuchi K.
,
Sawada K.
,
Nambu H.
,
Shogaki T.
and
Kita Y.
, Org. Lett. , 2003 , 5 , 3703
18.
Reddy N.K.
,
Vijaykumar B.V.
and
Chandrasekhar S.
, Org. Lett. , 2012 , 14 , 299
19.
Wakita H.
,
Yoshiwara H.
,
Nishiyama H.
and
Nagase H.
, Heterocycles , 2000 , 53 , 1085 .
20.
Liu X.
,
Tian C.
,
Jiao X.
,
Li X.
,
Yang H.
,
Yao Y.
and
Xie P.
, Org. Biomol. Chem. , 2016 , 14 , 7715 .
21.
Umemiya S.
,
Sakamoto D.
,
Kawauchi G.
and
Hayashi Y.
, Org. Lett ., 2017 , 19 , 1112 .
22.
Yang S.
,
Kang L.
and
Li Q.
, 2017 , P.R. China Patent: CN 106478572. Date of publication 8 March 2017 (patent not yet issued).
23.
Wakita H.
,
Matsumoto K.
,
Yoshiwara H.
,
Hosono Y.
,
Hayashi R.
and
Nagase H.
, Tetrahedron , 1999 , 55 , 2449 .
24.
Perlmutter P.
,
Selajerern W.
and
Vounatsos F.
, Org. Biomol. Chem. , 2004 , 2 , 2220 .