4-Hydroxybenzoic Acid → HCID 9842208, compound

HRID 854289Notes

Reaction equation

HRID 854289 reaction equation
[OH:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[CH:4][CH:3]=1.O.ON1C2C=CC=CC=2N=N1.[NH2:22][CH2:23][CH:24]1[CH2:29][CH2:28][N:27]([C:30]([O:32][CH2:33][C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)=[O:31])[CH2:26][CH2:25]1.C(N(CC)CC)C.Cl.C(N=C=NCCCN(C)C)C>CN(C=O)C>[CH2:33]([O:32][C:30]([N:27]1[CH2:28][CH2:29][CH:24]([CH2:23][NH:22][C:6](=[O:8])[C:5]2[CH:4]=[CH:3][C:2]([OH:1])=[CH:10][CH:9]=2)[CH2:25][CH2:26]1)=[O:31])[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1

Participants

7

Reactant 5

HCID 1354-Hydroxybenzoic AcidHCID 8471TriethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 219554994-Aminomethyl-1-N-Cbz-piperidine

Product 1

HCID 9842208HCID 9842208, compoundYield 94%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a mixture of 4-hydroxybenzoic acid (2.5 g, 0.0182 mol), 1-hydroxybenzotriazole hydrate (3.33 g, 0.0218 mol), benzyl 4-(aminomethyl)piperidine-1-carboxylate (4.5 g, 0.0182 mol) and triethylamine (3.03 mL, 0.0218 mol) in DMF (30mL) was added 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (4.2 g, 0.0218 mol) and the mixture allowed to stir at rt for 18 h. The mixture was quenched into water (200 mL) and extracted with ethyl acetate (200 nL). The ethyl acetate extract was washed with 10% aqueous sodium bicarbonate (100 mL), brine (50 mL), dried over sodium sulfate, and filtered. The filtrate was concentrated in vacuo and the residue chromatographed on silica using 10–20% acetone/dichloromethane to give 6.3 g of 4-[(4-hydroxy-benzoylamino)-methyl]-piperidine-1-carboxylic acid benzyl ester as a foam. The foam was dissolved in hot isopropyl acetate (125 mL), filtered, and allowed to cool and crystallize. The reaction volume was reduced in vacuo to 50 mL, allowed to stir overnight at rt and filtered. The resulting solid was dried in vacuo (50° C.) yielding the 4-[(4-hydroxy-benzoylamino)-methyl]-piperidine-1-carboxylic acid benzyl ester.

Workup

  1. customThe mixture was quenched into water (200 mL)
  2. extractionextracted with ethyl acetate (200 nL)
  3. extractionThe ethyl acetate extract
  4. washwas washed with 10% aqueous sodium bicarbonate (100 mL), brine (50 mL)
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationThe filtrate was concentrated in vacuo
  8. customthe residue chromatographed on silica using 10–20% acetone/dichloromethane

Sources & evidence

ORD record
ord-2a62fdd2140e4ff8bb8fd9d74415d9d1
Source dataset
uspto-grants-2007_08
Patent number
US07259157B2

Reaction notes

Loading…