4,4-Dimethylpentanoic acid → 1-(4,4-Dimethyl-pentanoyl)-4-(2-methoxy-ethyl)-piperidine-4-carboxylic acid ethyl ester

HRID 2194009Notes

Reaction equation

HRID 2194009 reaction equation
[CH3:1][C:2]([CH3:9])([CH3:8])[CH2:3][CH2:4][C:5]([OH:7])=O.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.[CH2:46]([O:48][C:49]([C:51]1([CH2:57][CH2:58][O:59][CH3:60])[CH2:56][CH2:55][NH:54][CH2:53][CH2:52]1)=[O:50])[CH3:47]>>[CH2:46]([O:48][C:49]([C:51]1([CH2:57][CH2:58][O:59][CH3:60])[CH2:52][CH2:53][N:54]([C:5](=[O:7])[CH2:4][CH2:3][C:2]([CH3:1])([CH3:9])[CH3:8])[CH2:55][CH2:56]1)=[O:50])[CH3:47]

Participants

5

Reactant 4

HCID 142374,4-Dimethylpentanoic acidHCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 567539694-(2-Methoxy-ethyl)-piperidine-4-carboxylic acid ethyl ester

Product 1

HCID 667874081-(4,4-Dimethyl-pentanoyl)-4-(2-methoxy-ethyl)-piperidine-4-carboxylic acid ethyl esterYield 52.8%

Procedure

To a solution of 4,4-dimethyl-pentanoic acid (0.351 g) in acetronitril (15 ml) were added under an argon atmosphere N-ethyldiisopropylamin (0.7 g, 0.96 ml) and BOP (1.195 g) and the mixture was stirred for 50 minutes at RT. Then 4-(2-methoxy-ethyl)-piperidine-4-carboxylic acid ethyl ester (0.581 g) was added and the mixture was stirred for further 12 h at RT. The reaction mixture was then 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-(4,4-dimethyl-pentanoyl)-4-(2-methoxy-ethyl)-piperidine-4-carboxylic acid ethyl ester (0.466 g) as a yellow semi-solid that was used in the next step without further purification.

Workup

  1. stirringthe mixture was stirred for further 12 h at RT
  2. customThe reaction mixture was then partitioned between ethyl acetate and aqueous 1M HCl
  3. customthe layers were separated
  4. washthe aqueous layer washed with 2M aqueous KHCO3
  5. dry with materialthen dried over Na2SO4
  6. customThe solvent was evaporated off
  7. customthe residue purified by flash chromatography (methylene chloride/AcOEt, gradient from 0 to 30%)

Sources & evidence

ORD record
ord-23a94f2d1a014a95bcc52f7a96eee6e8
Source dataset
uspto-grants-2012_12
Patent number
US08329904B2

Reaction notes

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