2,5-Dihydroxybenzoic acid → HCID 66746377, compound

HRID 514306Notes

Reaction equation

HRID 514306 reaction equation
[OH:1][C:2]1[CH:10]=[CH:9][C:8]([OH:11])=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].[CH3:12][NH:13][C@H:14]([CH2:16]/[CH:17]=[CH:18]/[C:19]1[CH:20]=[N:21][CH:22]=[C:23]([O:25][CH3:26])[CH:24]=1)[CH3:15].[OH:27][C:28]1[CH:36]=[CH:35][C:34]([OH:37])=[CH:33][C:29]=1[C:30]([OH:32])=[O:31].CN[C@H](C/C=C/C1C=NC=C(OC)C=1)C.C(OCC)(=O)C>C(O)C>[C:4]([OH:6])(=[O:5])[C:3]1[C:2](=[CH:10][CH:9]=[C:8]([CH:7]=1)[OH:11])[OH:1].[OH:27][C:28]1[CH:36]=[CH:35][C:34]([OH:37])=[CH:33][C:29]=1[C:30]([OH:32])=[O:31].[CH3:12][NH:13][C@H:14]([CH2:16]/[CH:17]=[CH:18]/[C:19]1[CH:20]=[N:21][CH:22]=[C:23]([O:25][CH3:26])[CH:24]=1)[CH3:15]

Participants

6

Reactant 4

HCID 34692,5-Dihydroxybenzoic acidHCID 8857Ethyl AcetateHCID 10262406552302-36-0HCID 11508769HCID 11508769, compound

Product 1

HCID 66746377HCID 66746377, compoundYield 91%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent3×

Procedure

(2S)-(4E)-N-Methyl-5-(5-methoxy-3-pyridinyl)-4-penten-2-amine 2,5-dihydroxybenzoate A hot solution of 2,5-dihydroxybenzoic acid (gentisic acid) (0.582 g, 3.78 mmol) in absolute ethanol (1 mL) was added to a warm solution of (2S)-(4E)-N-methyl-5-(5-methoxy-3-pyridinyl)-4-penten-2-amine (1.00 g, 4.85 mmol, 86.7% E isomer by GC-FID) in absolute ethanol (1 mL), using additional ethanol (2 mL) in the transfer. The resulting mixture was concentrated via rotary evaporation, leaving 1.5 mL of ethanol in the solution. With stirring and heating to near reflux, crystallization occurred. The resulting hot mixture was treated drop-wise with ethyl acetate (5.5 mL). After cooling to room temperature, the mixture was further cooled at 5° C. for 48 h. The resulting solids were filtered, washed with ethyl acetate (2×5 mL) and dried at 50° C. to give 1.24 g (91%) of an off-white powder (98.0% E isomer by GC-FID for the free base). To remove the color from the sample, the material was recrystallized from ethanol/isopropanol (3.5 mL: 5.5 mL) to give 1.03 g (83% recovery) of an off-white powder and subsequently recrystallized from ethanol/ethyl acetate (3 mL: 12 mL) to give 0.90 g (87% recovery) of a white, crystalline powder, mp 166-167° C.

Workup

  1. concentrationThe resulting mixture was concentrated via rotary evaporation
  2. customleaving 1.5 mL of ethanol in the solution
  3. temperatureheating to near reflux, crystallization
  4. temperaturethe mixture was further cooled at 5° C. for 48 h
  5. filtrationThe resulting solids were filtered
  6. washwashed with ethyl acetate (2×5 mL)
  7. customdried at 50° C.

Sources & evidence

ORD record
ord-887f768784c54bca996171f57a95a154
Source dataset
uspto-grants-2015_08
Patent number
US09107915B2

Reaction notes

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