Thionyl Chloride → (1S,4S)-4-(2,5-dimethyl-1H-pyrrol-1-yl)-1-isopropylcyclopent-2-enecarboxylic acid
Reaction equation
[NH2:1][C@H:2]1[CH2:6][C@@H:5]([C:7]([OH:9])=[O:8])[CH:4]=[CH:3]1.S(Cl)(Cl)=O.[CH3:14][C:15]1N([C@H]2C[C@@H](C(OC)=O)C=C2)[C:17]([CH3:20])=[CH:18][CH:19]=1.CO[C:32]([C@@H:34]1C[C@H](N)C=[CH:35]1)=O.CC(=O)CC(=O)C.CCN(C(C)C)C(C)C.ICCC.C[Si]([N-][Si](C)(C)C)(C)C.[Li+]>CO>[CH3:14][C:15]1[N:1]([C@H:2]2[CH2:6][C@@:5]([CH:34]([CH3:35])[CH3:32])([C:7]([OH:9])=[O:8])[CH:4]=[CH:3]2)[C:17]([CH3:20])=[CH:18][CH:19]=1Participants
10
Reactant 8
HCID 24386Thionyl Chloride
HCID 31261Acetylacetone
HCID 336431-Iodopropane
HCID 81531Diisopropylethylamine
HCID 2733832Lithium Hexamethyldisilazide
HCID 2734525(1R,4S)-4-Aminocyclopent-2-ene-1-carboxylic acid
HCID 11412436(1R,4S)-methyl 4-aminocyclopent-2-enecarboxylate
HCID 59700297(1R,4S)-methyl 4-(2,5-dimethyl-1H-pyrrol-1-yl)cyclopent-2-enecarboxylate2×Product 1
Reagents, catalysts & solvents 1
Procedure
Here, (1R,4S)-4-aminocyclopent-2-ene-1-carboxylic acid is converted into the corresponding methyl ester by treatment with thionyl chloride in methanol. Methyl (1R,4S)-4-(2,5-dimethyl-1H-pyrrol-1-yl)cyclopent-2-ene-1-carboxylate is then synthesized by reacting the (1R,4S)-4-aminocyclopent-2-ene-1-carboxylate methyl ester with 2,4-pentanedione in the presence of DIEA. The following alkylation of methyl (1R,4S)-4-(2,5-dimethyl-1H-pyrrol-1-yl)cyclopent-2-ene-1-carboxylate with iodopropane is carried out using lithium bis-(trimethylsilyl)amide as a base. The resulting alkylated product is then hydrolyzed to form the (1S,4S)-4-(2,5-dimethyl-1H-pyrrol-1-yl)-1-isopropylcyclopent-2-ene-1-carboxylic acid 4.
Sources & evidence
- ORD record
- ord-202b4032a5b049dbbec15d9065cd20d0
- Source dataset
- uspto-grants-2009_01
- Patent number
- US07473696B2
Reaction notes
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