Lithium Hydroxide → 4-[2-[4-[[4-(4-Chlorophenoxy)phenyl]amino]-1-piperidinyl]ethyl]benzoic acid

HRID 16524Notes

Reaction equation

HRID 16524 reaction equation
FC(F)(F)C(O)=O.[Cl:8][C:9]1[CH:40]=[CH:39][C:12]([O:13][C:14]2[CH:19]=[CH:18][C:17]([NH:20][CH:21]3[CH2:26][CH2:25][N:24]([CH2:27][CH2:28][C:29]4[CH:38]=[CH:37][C:32]([C:33]([O:35]C)=[O:34])=[CH:31][CH:30]=4)[CH2:23][CH2:22]3)=[CH:16][CH:15]=2)=[CH:11][CH:10]=1.[OH-].[Li+].C(O)(C(F)(F)F)=O>C1COCC1.CO.O>[Cl:8][C:9]1[CH:40]=[CH:39][C:12]([O:13][C:14]2[CH:15]=[CH:16][C:17]([NH:20][CH:21]3[CH2:26][CH2:25][N:24]([CH2:27][CH2:28][C:29]4[CH:30]=[CH:31][C:32]([C:33]([OH:35])=[O:34])=[CH:37][CH:38]=4)[CH2:23][CH2:22]3)=[CH:18][CH:19]=2)=[CH:11][CH:10]=1

Participants

7

Reactant 3

HCID 3939Lithium HydroxideHCID 6422Trifluoroacetic acidHCID 68490385HCID 68490385, compound

Product 1

HCID 236422164-[2-[4-[[4-(4-Chlorophenoxy)phenyl]amino]-1-piperidinyl]ethyl]benzoic acidYield 81.3%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of methyl 4-[2-[4-[[4-(4-chlorophenoxy)phenyl]amino]-1-piperidinyl]ethyl]benzoate trifluoroacetic acid salt (0.13 g, 0.18 mmol) in THF (4 mL) and methanol was stirred as an aqueous solution of lithium hydroxide (84 mg, 2 mmol) in 4 mL of water was added. The reaction was stirred for 17 hours and acidified with TFA. Purification by reverse phase preparative HPLC using a gradient of acetonitrile in water (plus 0.1% TFA) gave 66 mg of 4-[2-[4-[[4-(4-chlorophenoxy)phenyl]amino]-1-piperidinyl]ethyl]benzoic acid; 1H NMR (400 MHz, DMSO-d6) δ 7.85 (d, 2H), 7.44 (d, 2H), 7.35 (d, 2H), 6.86 (d, 4H), 6.64 (d, 2H), 3.62 (dbr, 2H), 3.37 (m, 3H), 3.08 (m, 4H), 2.14 (dbr, 2H), 1.56 (qbr, 2H) ppm.

Workup

  1. additionwas added
  2. customPurification by reverse phase preparative HPLC

Sources & evidence

ORD record
ord-34ff7a12d8ae408aacadbeff99d5959f
Source dataset
uspto-grants-2010_06
Patent number
US07737145B2

Reaction notes

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