Methanol → HCID 71252146, compound

HRID 2411230Notes

Reaction equation

HRID 2411230 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[CH:18][C:17]([C:20](OC)=[O:21])=[CH:16][C:15]=2[CH3:24])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].C([Al+]CC(C)C)C(C)C.CO.[C@H](O)(C([O-])=O)[C@@H](O)C([O-])=O.[Na+].[K+]>C(OCC)C>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][N:11]([C:14]2[CH:19]=[CH:18][C:17]([CH2:20][OH:21])=[CH:16][C:15]=2[CH3:24])[CH2:12][CH2:13]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 887MethanolHCID 9357Potassium Sodium TartrateHCID 21225700DiisobutylaluminumhydrideHCID 67048475HCID 67048475, compound

Product 1

HCID 71252146HCID 71252146, compoundYield 55.3%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
-78 °C

Procedure

The intermediate 4-(4-methoxycarbonyl-2-methylphenyl)piperazine-1-carboxylic acid tert-butyl ester (1.42 g) described in Preparation Example 97 was dissolved in diethyl ether (18 mL), 0.99M diisobutylaluminum hydride (9 mL) was added under cooling to −78° C., and the mixture was stirred while rising the temperature to room temperature. The mixture was further stirred at room temperature for 2 hr, methanol (0.7 mL) was added, and aqueous solution (5 mL) of Rochelle salt was added. The precipitate was collected by filtration from the reaction mixture, and the filtrate was concentrated. The obtained residue was purified by column chromatography (ethyl acetate:hexane) to give 4-(4-hydroxymethyl-2-methylphenyl)piperazine-1-carboxylic acid tert-butyl ester (720 mg). The obtained 4-(4-hydroxymethyl-2-methylphenyl)piperazine-1-carboxylic acid tert-butyl ester (720 mg) was dissolved in chloroform (6 mL), 4N hydrogen chloride/ethyl acetate solution (2.3 mL) was added, and the mixture was stirred at room temperature overnight. The reaction mixture was neutralized with aqueous potassium carbonate solution, and the mixture was extracted with ethyl acetate. The solvent was evaporated from the organic layer to give the title compound (654 mg).

Workup

  1. customto room temperature
  2. stirringThe mixture was further stirred at room temperature for 2 hr
  3. filtrationThe precipitate was collected by filtration from the reaction mixture
  4. concentrationthe filtrate was concentrated
  5. customThe obtained residue was purified by column chromatography (ethyl acetate:hexane)

Sources & evidence

ORD record
ord-846fcf82ddb44fb5b31f158b9b67c2fe
Source dataset
uspto-grants-2014_08
Patent number
US08816079B2

Reaction notes

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