Triethylamine → (+/-)-2-[(Acetylthio)methyl]-4-methyl-N-[2-(1-piperidinyl)ethyl]pentanamide

HRID 444194Notes

Reaction equation

HRID 444194 reaction equation
[C:1]([S:4][CH2:5][CH:6]([CH2:10][CH:11]([CH3:13])[CH3:12])[C:7]([OH:9])=O)(=[O:3])[CH3:2].C(N(CC)CC)C.ClC(OCC)=O.[NH2:27][CH2:28][CH2:29][N:30]1[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]1>C1COCC1>[C:1]([S:4][CH2:5][CH:6]([CH2:10][CH:11]([CH3:13])[CH3:12])[C:7]([NH:27][CH2:28][CH2:29][N:30]1[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]1)=[O:9])(=[O:3])[CH3:2]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 10928Ethyl chloroformateHCID 33944N-(2-Aminoethyl)piperidineHCID 130175572-[(Acetylthio)methyl]-4-methylpentanoic acid

Product 1

HCID 13017560(+/-)-2-[(Acetylthio)methyl]-4-methyl-N-[2-(1-piperidinyl)ethyl]pentanamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent4×

Conditions

Temperature
-5 °C

Procedure

A solution of (±)-2-[(acetylthio)methyl]-4-methylpentanoic acid in 40 ml of THF is cooled to 5° C., followed by the dropwise addition of triethylamine (1.0 g) in 5 ml of THF. This solution is cooled to -5° C. and ethyl chloroformate in 4 ml of THF is added dropwise at -5° to 0° C. It is stirred for 30 minutes and N-(2-aminoethyl)piperidine in 30 ml of THF is added dropwise. The reaction mixture is stirred at 20° C. for 4 hours and stored at 0° C. for about 16 hours. Triethylamine hydrochloride is filtered off and the filtrate is concentrated in vacuo. The residue is dissolved in ether and washed with aqueous NaHCO3. Ether is dried with MgSO4, filtered and concentrated in vacuo to yield 2.1 g of crude product. This crude is absorbed on a 20-g pad of alumina act II and washed through with ether to yield 1.4 g of product which crystallizes from pentane, melting point 47°-50° C.

Workup

  1. stirringThe reaction mixture is stirred at 20° C. for 4 hours
  2. waitstored at 0° C. for about 16 hours
  3. filtrationTriethylamine hydrochloride is filtered off
  4. concentrationthe filtrate is concentrated in vacuo
  5. dissolutionThe residue is dissolved in ether
  6. washwashed with aqueous NaHCO3
  7. dry with materialEther is dried with MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customto yield 2.1 g of crude product
  11. customThis crude is absorbed on a 20-g pad of alumina act II
  12. washwashed through with ether

Sources & evidence

ORD record
ord-c459f6f524b44b9497a322d4f31028e8
Source dataset
uspto-grants-1981_04
Patent number
US04263293

Reaction notes

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