Methylparaben → HCID 178498290, compound

HRID 1984025Notes

Reaction equation

HRID 1984025 reaction equation
[CH:1]([N:4]1[CH2:9][CH2:8][N:7]([C:10]([C@H:12]2[CH2:17][CH2:16][C@@H:15]([OH:18])[CH2:14][CH2:13]2)=[O:11])[CH2:6][CH2:5]1)([CH3:3])[CH3:2].O[C:20]1[CH:29]=[CH:28][C:23]([C:24]([O:26][CH3:27])=[O:25])=[CH:22][CH:21]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)(C)C)=O)=NC(OC(C)(C)C)=O>C1COCC1>[CH3:27][O:26][C:24](=[O:25])[C:23]1[CH:28]=[CH:29][C:20]([O:18][C@H:15]2[CH2:14][CH2:13][C@H:12]([C:10]([N:7]3[CH2:8][CH2:9][N:4]([CH:1]([CH3:3])[CH3:2])[CH2:5][CH2:6]3)=[O:11])[CH2:17][CH2:16]2)=[CH:21][CH:22]=1

Participants

6

Reactant 4

HCID 7456MethylparabenHCID 11776TriphenylphosphineHCID 97268Di-tert-butyl azodicarboxylateHCID 178456387HCID 178456387, compound

Product 1

HCID 178498290HCID 178498290, compoundYield 25%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

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. additionwas added dropwise at 0° C.
  2. customAfter evaporation
  3. customthe residue was purified by column chromatography on silica gel eluting with CH2Cl2 and methanol=from 98:2 to 9:1
  4. customAfter evaporation of the combined products
  5. customthe residue was purified by column chromatography on silica gel eluting with CH2Cl2 and MeOH=from 100:0 to 19:1
  6. customThe combined product fractions were evaporated to dryness

Sources & evidence

ORD record
ord-b74997cff2d54ae2a1956123263c18a6
Source dataset
uspto-grants-2009_06
Patent number
US07544683B2

Reaction notes

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