Diisopropylethylamine → 1-(3-Cyclopropyl-propionyl)-4-(2-methoxy-ethyl)-piperidine-4-carboxylic acid ethyl ester
Reaction equation
[CH:1]1([CH2:4][CH2:5][C:6]([OH:8])=O)[CH2:3][CH2:2]1.C(N(C(C)C)C(C)C)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.[CH2:45]([O:47][C:48]([C:50]1([CH2:56][CH2:57][O:58][CH3:59])[CH2:55][CH2:54][NH:53][CH2:52][CH2:51]1)=[O:49])[CH3:46]>>[CH2:45]([O:47][C:48]([C:50]1([CH2:56][CH2:57][O:58][CH3:59])[CH2:51][CH2:52][N:53]([C:6](=[O:8])[CH2:5][CH2:4][CH:1]2[CH2:2][CH2:3]2)[CH2:54][CH2:55]1)=[O:49])[CH3:46]Participants
Reactant 4
Product 1
Procedure
To a solution of 3-cyclopropyl-propionic acid (0.342 g) in acetronitril (15 ml) were added under an argon atmosphere N-ethyldiisopropylamine (0.775 g, 1.03 ml) and BOP (1.328 g and the mixture was stirred for 50 minutes at RT. Then 4-(2-methoxy-ethyl)-piperidine-4-carboxylic acid ethyl ester (0.646 g) were added and the mixture was stirred for 12 h at RT. The reaction mixture was partitioned between ethyl acetate and aqueous 1M HCl, the layers were separated and the aqueous layer washed with 2M aqueous KHCO3 then dried over Na2SO4. The solvent was evaporated off, the residue purified by flash chromatography (methylene chloride/AcOEt, gradient from 0 to 30%) to give 1-(3-cyclopropyl-propionyl)-4-(2-methoxy-ethyl)-piperidine-4-carboxylic acid ethyl ester, (0.34 g) as a yellow oil that was used in the next step without further purification.
Workup
- stirringthe mixture was stirred for 12 h at RT
- customThe reaction mixture was partitioned between ethyl acetate and aqueous 1M HCl
- customthe layers were separated
- washthe aqueous layer washed with 2M aqueous KHCO3
- dry with materialthen dried over Na2SO4
- customThe solvent was evaporated off
- customthe residue purified by flash chromatography (methylene chloride/AcOEt, gradient from 0 to 30%)
Sources & evidence
- ORD record
- ord-9da3f4c11b0c4e41bd7ba5d34fdfab76
- Source dataset
- uspto-grants-2012_12
- Patent number
- US08329904B2
Reaction notes
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