Water → HCID 178456385, compound

HRID 1984026Notes

Reaction equation

HRID 1984026 reaction equation
C[O:2][C:3](=[O:28])[C:4]1[CH:9]=[CH:8][C:7]([O:10][C@H:11]2[CH2:16][CH2:15][C@H:14]([C:17]([N:19]3[CH2:24][CH2:23][N:22]([CH:25]([CH3:27])[CH3:26])[CH2:21][CH2:20]3)=[O:18])[CH2:13][CH2:12]2)=[CH:6][CH:5]=1.[OH-].[Li+].C1COCC1.O>CO>[CH:25]([N:22]1[CH2:21][CH2:20][N:19]([C:17]([C@H:14]2[CH2:13][CH2:12][C@H:11]([O:10][C:7]3[CH:6]=[CH:5][C:4]([C:3]([OH:28])=[O:2])=[CH:9][CH:8]=3)[CH2:16][CH2:15]2)=[O:18])[CH2:24][CH2:23]1)([CH3:27])[CH3:26]

Participants

6

Reactant 4

HCID 962WaterHCID 3939Lithium HydroxideHCID 8028TetrahydrofuranHCID 178498290HCID 178498290, compound

Product 1

HCID 178456385HCID 178456385, compoundYield 99.7%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
80 °C

Procedure

To a mixture 3.5 g (13.8 mmol) of cis-(4-Isopropyl-piperazin-1-yl)-(4-hydroxycyclohexyl)-methanone, 2.35 g (15.4 mmol) of methyl 4-hydroxybenzoate, 4.47 g (17.0 mmol) of triphenylphosphine in 12 ml of THF, a mixture of 3.88 g (16.9 mmol) of di-tert-butyl azodicarboxylate in 13 ml of THF was added dropwise at 0° C., and stirred for 24 h at room temperature. After evaporation, the residue was purified by column chromatography on silica gel eluting with CH2Cl2 and methanol=from 98:2 to 9:1. After evaporation of the combined products, the residue was purified by column chromatography on silica gel eluting with CH2Cl2 and MeOH=from 100:0 to 19:1. The combined product fractions were evaporated to dryness to yield 1.34 g (25%) of trans-4-[4-(4-Isopropyl-piperazine-1-carbonyl)-cyclohexyloxy]-benzoic acid methyl ester. A mixture of 0.6 g (1.5 mmol) of trans-4-[4-(4-Isopropyl-piperazine-1-carbonyl)-cyclohexyloxy]-benzoic acid methyl ester, 42 mg (1.8 mmol) of lithium hydroxide, 6 ml of THF, 3 ml of water, and 1 ml of methanol was stirred at 80° C. for 16 h. After evaporation, the residue was acidified with 2N hydrochloric acid solution and evaporated. The precipitate was washed with water and dried to yield 0.56 g (97%) of the titled compound. MS (m/e): 375 (MH+).

Workup

  1. customAfter evaporation
  2. customevaporated
  3. washThe precipitate was washed with water
  4. customdried

Sources & evidence

ORD record
ord-464f7eddded240e8a5ab3abad4b03e41
Source dataset
uspto-grants-2009_06
Patent number
US07544683B2

Reaction notes

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