Hydrochloric Acid → Cyclohexanecarboxylic Acid (4-hydroxy-benzyl)-[4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-amide

HRID 1827526Notes

Reaction equation

HRID 1827526 reaction equation
[N:1]1([CH2:6][CH2:7][O:8][C:9]2[CH:14]=[CH:13][C:12]([N:15]([CH2:24][C:25]3[CH:30]=[CH:29][C:28]([O:31]C4CCCCO4)=[CH:27][CH:26]=3)[C:16]([CH:18]3[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]3)=[O:17])=[CH:11][CH:10]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.C1(C)C=CC(S([O-])(=O)=O)=CC=1.[NH+]1C=CC=CC=1.Cl>C(O)C>[OH:31][C:28]1[CH:27]=[CH:26][C:25]([CH2:24][N:15]([C:12]2[CH:13]=[CH:14][C:9]([O:8][CH2:7][CH2:6][N:1]3[CH2:5][CH2:4][CH2:3][CH2:2]3)=[CH:10][CH:11]=2)[C:16]([CH:18]2[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]2)=[O:17])=[CH:30][CH:29]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 466102Benzenesulfonic acid, 4-methyl-, compd. with pyridine (1:1)HCID 86592784Cyclohexanecarboxylic acid [4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-[4-(tetrahydro-pyran-2-yloxy)-benzyl]-amide

Product 1

HCID 9845153Cyclohexanecarboxylic Acid (4-hydroxy-benzyl)-[4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-amideYield 84.7%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of cyclohexanecarboxylic acid [4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-[4-(tetrahydro-pyran-2-yloxy)-benzyl]-amide (1.64 g, 3.24 mmol), pyridinium p-toluenesulfonate (85 mg, 0.32 mmmol) and ethanol (30 mL) was stirred at room temperature for 24 hr. Aqueous 1N HCl (10 mL) was added and the reaction was stirred for 3–4 hr. The reaction mixture was concentrated to 1/3 the volume and saturated aqueous sodium bicarbonate was added. The aqueous solution was washed with methylene chloride and the organic solution was dried (magnesium sulfate), filtered, and concentrated. Medium pressure chromatography using a solvent gradient (3% methanol in methylene chloride to 15% methanol in methylene chloride) provided the title compound as a white solid (1.16 g). The solid was suspended in methanol (15 mL) and 1.4 mL of 4N HCl in dioxane was added dropwise. The reaction was stirred at room temperature for 0.5 hr. and was concentrated to provide the title compound as the hydrochloride salt. MS 423.2 (M+1)+

Workup

  1. stirringthe reaction was stirred for 3–4 hr
  2. concentrationThe reaction mixture was concentrated to 1/3 the volume and saturated aqueous sodium bicarbonate
  3. additionwas added
  4. washThe aqueous solution was washed with methylene chloride
  5. dry with materialthe organic solution was dried (magnesium sulfate)
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-69b925cc8fb44b23aeeb86dfe96f8f31
Source dataset
uspto-grants-2006_05
Patent number
US07053212B2

Reaction notes

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