Rolipram → 4-[3-(Benzyloxy)-4-methoxyphenyl]pyrrolidin-2-one
Reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH:15]2[CH2:20][NH:19][C:17](=[O:18])[CH2:16]2)=[CH:7][C:8]=1[O:9][CH:10]1[CH2:14][CH2:13][CH2:12][CH2:11]1.CO[C:23]1C=CC([C@H]2CNC(=O)C2)=C[C:24]=1OC1CCCC1.C(OC)(=O)CC([O-])=O>>[CH2:10]([O:9][C:8]1[CH:7]=[C:6]([CH:15]2[CH2:20][NH:19][C:17](=[O:18])[CH2:16]2)[CH:5]=[CH:4][C:3]=1[O:2][CH3:1])[C:14]1[CH:13]=[CH:12][CH:11]=[CH:24][CH:23]=1Participants
Procedure
The compounds of the present invention may be prepared conventionally. Some of the known processes that can be used are described below. All starting materials are known or can be conventionally prepared from known starting materials. Preparation of Starting Material (Scheme I) Enantiomerically pure rolipram, 4-(3-cyclopentyloxy-4-methoxyphenyl)-2-pyrrolidone, and the starting material 4-(3-benzyloxy-4-methoxyphenyl)-2-pyrrolidone were prepared as shown in scheme I and in a similar fashion as described previously (J. Demnitz, et. al., Enantiodivergent synthesis of (R)-and (S)-Rolipram, Molecules, 1998, 3, 107-119). Thus, appropriately substituted benzaldehydes were condensed with monomethyl malonate to provide the corresponding methyl cinnamyl esters after decarboxylation. Conjugate addition of nitromethane using tetramethyl guanidine as base provided methyl 4-nitro-3-(substituted-phenyl)butyrate. Racemic 4-(3-benzyloxy-4-methoxyphenyl)-2-pyrrolidone was produced in 85% yield by selective reduction of the nitro group to the corresponding amine using NiCl2 and NaBH4 (Osby, J. O.; Ganem, B., Rapid and efficient reduction of aliphatic nitro compounds to amines, Tetrahedron Lett., 1985, 26, 6413-6416) and subsequent treatment with K2CO3.
Workup
- customThe compounds of the present invention may be prepared conventionally
- customcan be conventionally prepared
Sources & evidence
- ORD record
- ord-3a362ed7fb3b4ea9931bf5ea3fe5052e
- Source dataset
- uspto-grants-2007_06
- Patent number
- US07235579B2
Reaction notes
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