Trifluoroacetic acid → HCID 59402458, compound

HRID 655784Notes

Reaction equation

HRID 655784 reaction equation
[CH2:1]([O:4][CH:5]1[CH2:10][CH2:9]CCN1C([O-])=O)CC.[C:14](O)([C:16](F)(F)F)=[O:15].[Cl:21][C:22]1[CH:23]=[C:24]([C:28]([OH:30])=O)[NH:25][C:26]=1[CH3:27].C1C=CC2N([OH:40])N=NC=2C=1.CN1CCOCC1.Cl.C(N=C=[N:53][CH2:54][CH2:55][CH2:56][N:57]([CH3:59])[CH3:58])C>ClCCl>[Cl:21][C:22]1[CH:23]=[C:24]([C:28]([NH:53][C@@H:54]2[CH2:55][CH2:56][N:57]([C:58]([O:15][CH2:14][CH3:16])=[O:40])[CH2:59][C@@H:1]2[O:4][CH2:5][CH2:10][CH3:9])=[O:30])[NH:25][C:26]=1[CH3:27]

Participants

8

Reactant 6

HCID 6422Trifluoroacetic acidHCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 251376814-Chloro-5-methyl-1H-pyrrole-2-carboxylic acid2×HCID 131729302HCID 131729302, compound2×

Product 1

HCID 59402458HCID 59402458, compoundYield 84%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Ethyl-(3S,4R)-4-[(tert-butoxycarbonyl)amino]-3-(propyoxypiperidine-1-carboxylate (Intermediate 72, 3 g) was treated with TFA (5 mL) for 30 min and the concentrated under reduced pressure. The resulting residue was dissolved in dichloromethane (150 mL) with 4-chloro-5-methyl-1H-pyrrole-2-carboxylic acid (Intermediate 27, 1.45 g, 9.13 mmol), HOBT (1.676 g, 10.95 mmol) and N-methyl morpholine (2.76 g, 27.39 mmol). The reaction mixture was stirred for 1 h at room temperature and 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (3.02 g, 16.43 mmol) was added. The resulting reaction mixture was stirred at room temperature overnight. The reaction mixture was quenched with 2N hydrochloric acid (30 mL) and the layers were separated. The organic layer was washed with sodium bicarbonate (40 mL), water (60 mL) and finally with brine successively and dried over anhydrous sodium sulphate, filtered, and concentrated under vacuum to afford ethyl (3S,4R)-4-{[(4-chloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-propoxypiperidine-1-carboxylate 2.8 g (84%) as solid.

Workup

  1. concentrationthe concentrated under reduced pressure
  2. customThe resulting reaction mixture
  3. stirringwas stirred at room temperature overnight
  4. customThe reaction mixture was quenched with 2N hydrochloric acid (30 mL)
  5. customthe layers were separated
  6. washThe organic layer was washed with sodium bicarbonate (40 mL), water (60 mL) and finally with brine successively
  7. dry with materialdried over anhydrous sodium sulphate
  8. filtrationfiltered
  9. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-05c052510f9742f8a13acf38e54d7923
Source dataset
uspto-grants-2011_12
Patent number
US08071605B2

Reaction notes

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