1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 1-[2-(5-fluoro-1,3-dihydro-2H-isoindol-2-yl)-2-oxoethyl]-3-phenylpiperidin-2-one

HRID 1667181Notes

Reaction equation

HRID 1667181 reaction equation
[O:1]=[C:2]1[CH:7]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH2:6][CH2:5][CH2:4][N:3]1[CH2:14][C:15]([OH:17])=O.Cl.[F:19][C:20]1[CH:21]=[C:22]2[C:26](=[CH:27][CH:28]=1)[CH2:25][NH:24][CH2:23]2.C(N=C=NCCCN(C)C)C>ClCCl>[F:19][C:20]1[CH:21]=[C:22]2[C:26](=[CH:27][CH:28]=1)[CH2:25][N:24]([C:15](=[O:17])[CH2:14][N:3]1[CH2:4][CH2:5][CH2:6][CH:7]([C:8]3[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=3)[C:2]1=[O:1])[CH2:23]2

Participants

5

Reactant 3

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 179862865-fluoro-2,3-dihydro-1H-isoindole hydrochlorideHCID 673587022-(2-Oxo-3-phenylpiperidin-1-yl)acetic acid

Product 1

HCID 452754971-[2-(5-fluoro-1,3-dihydro-2H-isoindol-2-yl)-2-oxoethyl]-3-phenylpiperidin-2-one

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To 2-(2-oxo-3-phenylpiperidin-1-yl)acetic acid (Example 91D, 0.168 g, 0.720 mmol) and 5-fluoroisoindoline hydrochloride (0.138 g, 0.792 mmol) in dichloromethane (0.5 mL) was added N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine (0.191 mL, 1.080 mmol), and the reaction was stirred at ambient temperature overnight. The reaction was loaded directly onto a SF15-12 silica gel column (Analogix®, Burlington, Wis.), and the title compound was eluted using a gradient of 5% to 100% ethyl acetate/hexanes over 20 minutes (flow=30 mL/minute). 1H NMR (300 MHz, CDCl3) δ ppm 7.14-7.36 (m, 6H), 6.92-7.02 (m, 2H), 4.85-4.90 (m, 2H), 4.78-4.83 (m, 2H), 4.43 (dd, J=15.6, 1.7 Hz, 1H), 4.06 (d, J=15.7 Hz, 1H), 3.73 (dd, J=7.7, 6.1 Hz, 1H), 3.65-3.71 (m, 1H), 3.57 (dt, J=11.6, 5.8 Hz, 1H), 2.19-2.29 (m, 1H), 1.97-2.11 (m, 2H), 1.83-2.00 (m, 1H); MS (DCI+) m/z 353 (M+H)+.

Workup

  1. washthe title compound was eluted
  2. customover 20 minutes

Sources & evidence

ORD record
ord-6fb9645cd97d4e6eaca9d9fce0662e2c
Source dataset
uspto-grants-2011_10
Patent number
US08044069B2

Reaction notes

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