Potassium Hydroxide → HCID 87998637, compound

HRID 895347Notes

Reaction equation

HRID 895347 reaction equation
[CH3:1][O:2][C:3](=[O:39])[C:4]1[CH:9]=[CH:8][C:7]([CH:10]([N:28]2[CH2:33][CH2:32][N:31]([CH2:34][C:35]([O:37]C)=[O:36])[CH2:30][CH2:29]2)[CH2:11][O:12][CH2:13][C:14]2[CH:19]=[C:18]([C:20]([F:23])([F:22])[F:21])[CH:17]=[C:16]([C:24]([F:27])([F:26])[F:25])[CH:15]=2)=[CH:6][CH:5]=1.[OH-].[K+]>CO>[OH2:2].[CH3:1][O:2][C:3](=[O:39])[C:4]1[CH:5]=[CH:6][C:7]([CH:10]([N:28]2[CH2:29][CH2:30][N:31]([CH2:34][C:35]([OH:37])=[O:36])[CH2:32][CH2:33]2)[CH2:11][O:12][CH2:13][C:14]2[CH:19]=[C:18]([C:20]([F:22])([F:23])[F:21])[CH:17]=[C:16]([C:24]([F:25])([F:26])[F:27])[CH:15]=2)=[CH:8][CH:9]=1.[F:23][C:20]([C:18]1[CH:19]=[C:14]([CH:15]=[C:16]([C:24]([F:25])([F:26])[F:27])[CH:17]=1)[CH2:13][O:12][CH2:11][CH:10]([C:7]1[CH:6]=[CH:5][C:4]([C:3]([O:2][CH3:1])=[O:39])=[CH:9][CH:8]=1)[N:28]1[CH2:33][CH2:32][N:31]([CH2:34][C:35]([OH:37])=[O:36])[CH2:30][CH2:29]1)([F:22])[F:21]

Participants

4

Reactant 2

HCID 14797Potassium HydroxideHCID 86590286HCID 86590286, compound2×

Product 1

HCID 87998637HCID 87998637, compoundYield 104.6%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Conditions

Temperature
0 °C

Procedure

In a round-bottomed flask was introduced 4-[2-(3,5-Bis-trifluoromethyl-benzyloxy)-1-(4-methoxycarbonylmethyl-piperazin-1-yl)-ethyl]-benzoic acid methyl ester (compound 316 prepared at example 2 above; 2.17 g, 3.86 mmoles) dissolved in MeOH (30 ml). To this solution cooled at 0° C. was added KOH (0.54 g, 9.62 mmoles) dissolved in MeOH (20 ml). The reaction mixture was allowed to stand at room temperature overnight. The reaction was cooled to 0° C., quenched by addition of HCl 0.1 N and extracted with CH2Cl2. The combined organic layers were dried over MgSO4 and concentrated. The residu was purified by chromatography on silica gel (eluent: CH2Cl2/MeOH/H2O: 95/5/0.5) to yield 4-[2-(3,5-bis-trifluoromethyl-benzyloxy)-1-(4-carboxymethyl-piperazin-1-yl)-ethyl]-benzoic acid methyl ester hemihydrate (compound 318; 1.5 g, 71%).

Workup

  1. temperatureThe reaction was cooled to 0° C.
  2. customquenched by addition of HCl 0.1 N
  3. extractionextracted with CH2Cl2
  4. dry with materialThe combined organic layers were dried over MgSO4
  5. concentrationconcentrated
  6. customThe residu was purified by chromatography on silica gel (eluent: CH2Cl2/MeOH/H2O: 95/5/0.5)

Sources & evidence

ORD record
ord-7bf4d132d6da4d7fb114ddbb473c396d
Source dataset
uspto-grants-2005_07
Patent number
US06916797B2

Reaction notes

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