Benzoic acid, 4-fluoro-, ethyl ester → 4-Benzylbenzoate piperidine 4-ethyl benzoate

HRID 2190555Notes

Reaction equation

HRID 2190555 reaction equation
[CH2:1]([O:8][C:9](=[O:22])[C:10]1[CH:15]=[CH:14][C:13]([N:16]2[CH2:21][CH2:20]NCC2)=[CH:12][CH:11]=1)[C:2]1C=CC=CC=1.C([O:25][C:26](=[O:34])[C:27]1[CH:32]=[CH:31][C:30](F)=[CH:29][CH:28]=1)C.C(N(C(C)C)CC)(C)C>CN(C1C=CN=CC=1)C.CS(C)=O>[CH2:26]([C:13]1[CH:12]=[CH:11][C:10]([C:9]([O-:8])=[O:22])=[CH:15][CH:14]=1)[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.[NH:16]1[CH2:13][CH2:14][CH2:15][CH2:20][CH2:21]1.[CH3:1][CH2:2][C:30]1[CH:29]=[CH:28][C:27]([C:26]([OH:25])=[O:34])=[CH:32][CH:31]=1

Participants

6

Reactant 3

HCID 67976Benzoic acid, 4-fluoro-, ethyl esterHCID 81531DiisopropylethylamineHCID 539216634-Piperazin-1-yl-benzoic acid benzyl ester

Product 1

HCID 1317300884-Benzylbenzoate piperidine 4-ethyl benzoateYield 128%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 679Dimethyl SulfoxideSolvent

Procedure

A mixture of 4-piperazin-1-yl-benzoic acid benzyl ester (500 mg, 1.68 mmol), 4-fluoro benzoic acid ethyl ester (1.4 g, 8.4 mmol), diisopropylethyl amine (1.47 mL, 8.4 mmol) and a catalytic amount of DMAP in DMSO (6 mL) was stirred at 130° C. in a sealed tube for 70 h. The mixture was the cooled partitioned between EtOAc and water. The EtOAc layer was collected, dried over Na2SO4, filtered and concentrated. The residue was suspended in hexanes and the suspension was then filtered. The solid obtained passed through a plug of silica gel using 0-100% EtOAc in hexanes to afford the product (480 mg, Yield; 64%). HRMS m/z calcd for C27H28N2O4 [M+H]+: 445.2122; Found: 445.2120.

Workup

  1. custompartitioned between EtOAc and water
  2. customThe EtOAc layer was collected
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. filtrationthe suspension was then filtered
  7. customThe solid obtained

Sources & evidence

ORD record
ord-965bb96018b546ef8eeba852a2b0688a
Source dataset
uspto-grants-2012_12
Patent number
US08324385B2

Reaction notes

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