4-Methylmorpholine → Ethyl (3S,4R)-4-{[(4-chloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-ethoxypiperidine-1-carboxylate

HRID 655768Notes

Reaction equation

HRID 655768 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:8]([OH:10])=O)[NH:5][C:6]=1[CH3:7].[NH2:11][C@@H:12]1[CH2:17][CH2:16][N:15]([C:18]([O:20][CH2:21][CH3:22])=[O:19])[CH2:14][C@@H:13]1[O:23][CH2:24][CH3:25].C1C=CC2N(O)N=NC=2C=1.CN1CCOCC1.CCN=C=NCCCN(C)C.Cl>ClCCl>[Cl:1][C:2]1[CH:3]=[C:4]([C:8]([NH:11][C@@H:12]2[CH2:17][CH2:16][N:15]([C:18]([O:20][CH2:21][CH3:22])=[O:19])[CH2:14][C@@H:13]2[O:23][CH2:24][CH3:25])=[O:10])[NH:5][C:6]=1[CH3:7]

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 251376814-Chloro-5-methyl-1H-pyrrole-2-carboxylic acid2×HCID 54237477Ethyl (3S,4R)-4-amino-3-ethoxypiperidine-1-carboxylate2×

Product 1

HCID 59402578Ethyl (3S,4R)-4-{[(4-chloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-ethoxypiperidine-1-carboxylateYield 80.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 4-chloro-5-methyl-1H-pyrrole-2-carboxylic acid (Intermediate 27, 0.87 g, 5.55 mol) and ethyl (3S,4R)-4-amino-3-ethoxypiperidine-1-carboxylate (Intermediate 24, 1.2 g, 5.55 mmol) in dichloromethane (150 mL) was added HOBT (850 mg, 0.55 mmol) and N-methyl morpholine (1.82 mL, 1.66 mmol). The reaction mixture was stirred for 1 h at room temperature and EDC HCl (1.9 g, 9.99 mmol) was added. The resulting reaction mixture was stirred at room temperature overnight. The reaction mixture was quenched with the addition of 2N HCl (120 mL). The organic layer was washed with sodium bicarbonate (150 mL), water (150 mL) and brine, dried over anhydrous sodium sulphate, filtered, concentrated under vacuum. Purification by column chromatography (silica, 35% ethyl acetate in pet ether) afforded Ethyl (3S,4R)-4-{[(4-chloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-ethoxypiperidine-1-carboxylate 1.6 g (80%) as brown solid.

Workup

  1. customThe resulting reaction mixture
  2. stirringwas stirred at room temperature overnight
  3. customThe reaction mixture was quenched with the addition of 2N HCl (120 mL)
  4. washThe organic layer was washed with sodium bicarbonate (150 mL), water (150 mL) and brine
  5. dry with materialdried over anhydrous sodium sulphate
  6. filtrationfiltered
  7. concentrationconcentrated under vacuum
  8. customPurification by column chromatography (silica, 35% ethyl acetate in pet ether)

Sources & evidence

ORD record
ord-9315d3826bff4c5384cfc45b47c7b72e
Source dataset
uspto-grants-2011_12
Patent number
US08071605B2

Reaction notes

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