N-[3-(4-Fluorophenyl)-3-oxopropyl]pipecolic acid methyl ester → N-[3-(4-chlorophenyl)-3-(4-fluorophenyl)3-hydroxypropyl]pipecolic acid methyl ester

HRID 635921Notes

Reaction equation

HRID 635921 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([Mg]I)=[CH:4][CH:3]=1.[CH3:10][O:11][C:12](=[O:30])[CH:13]1[CH2:18][CH2:17][CH2:16][CH2:15][N:14]1[CH2:19][CH2:20][C:21]([C:23]1[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=1)=[O:22]>C(OCC)C>[CH3:10][O:11][C:12](=[O:30])[CH:13]1[CH2:18][CH2:17][CH2:16][CH2:15][N:14]1[CH2:19][CH2:20][C:21]([C:5]1[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=1)([C:23]1[CH:24]=[CH:25][C:26]([F:29])=[CH:27][CH:28]=1)[OH:22]

Participants

4

Reactant 2

HCID 53681476N-[3-(4-Fluorophenyl)-3-oxopropyl]pipecolic acid methyl esterHCID 178478194HCID 178478194, compound

Product 1

HCID 16004955N-[3-(4-chlorophenyl)-3-(4-fluorophenyl)3-hydroxypropyl]pipecolic acid methyl esterYield 4.5%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Procedure

7 ml (2 mmol) of 0.28 M solution of 4-chlorophenylmagnesium iodide in diethyl ether [prepared from 1-chloro-4-iodobenzene (Aldrich) and magnesium] was added dropwise to an ice-cooled solution of 0.605 g (2 mmol) N-[3-(4-fluorophenyl)-3-oxopropyl]pipecolic acid methyl ester (from Step 1) in 12 ml anhydrous diethyl ether with stirring under nitrogen. The mixture was stirred at room temperature for 16 hours, poured onto crushed ice and extracted with dichloromethane. The combined organic extracts were washed with brine, concentrated and the residue purified by preparative silica gel TLC with 25% ethyl acetate in hexanes to give 0.037 g (yield 4.5%) N-[3-(4-chlorophenyl)-3-(4-fluorophenyl)3-hydroxypropyl]pipecolic acid methyl ester (Compound B30).

Workup

  1. stirringThe mixture was stirred at room temperature for 16 hours
  2. additionpoured
  3. customonto crushed ice
  4. extractionextracted with dichloromethane
  5. washThe combined organic extracts were washed with brine
  6. concentrationconcentrated
  7. customthe residue purified by preparative silica gel TLC with 25% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-075612c2b0b7443ab76286a1a825c0ea
Source dataset
uspto-grants-2001_02
Patent number
US06191165B1

Reaction notes

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