Hydrochloric Acid → HCID 11508247, compound

HRID 1394133Notes

Reaction equation

HRID 1394133 reaction equation
C(OC([N:8]1[CH2:12][C@@H:11]([CH2:13][NH:14][C:15](=[O:22])[C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH2:10][C@H:9]1[C:23]([N:25]1[CH2:29][CH2:28][S:27][CH2:26]1)=[O:24])=O)(C)(C)C.[H-].[Na+].CI.Cl.O1CCOC[CH2:36]1>CN(C=O)C.ClCCl>[CH3:36][N:14]([CH2:13][C@H:11]1[CH2:10][C@@H:9]([C:23]([N:25]2[CH2:29][CH2:28][S:27][CH2:26]2)=[O:24])[NH:8][CH2:12]1)[C:15](=[O:22])[C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 312751,4-DioxaneHCID 69241720HCID 69241720, compound

Product 1

HCID 11508247HCID 11508247, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of (2S, 4R)-4-(benzoylamino-methyl)-2-(thiazolidine-3-carbonyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (180 mg, 0.43 mmol) in anhydrous DMF (8 mL) was added sodium hydride (13 mg, 0.56 mmol) under nitrogen. The mixture stirred for 15 minutes followed by the addition of methyl iodide (0.04 mL, 0.64 mmol). The mixture was allowed to stir for 2 hours at room temperature, concentrated under reduced pressure, and the residue was partitioned between ethyl acetate (10 mL) and H2O (5 mL). The aqueous layer was extracted with ethyl acetate (2×10 mL), and the combined organic layers were dried (Na2SO4), filtered, and concentrated under reduced pressure to provide a yellow oil. To a solution of the oil in dichloromethane (10 mL) was added a solution of 4N HCl in dioxane (2 mL, 8 mmol) and the mixture was allowed to stir for 12 hours at room temperature. The mixture was concentrated under reduced pressure and the residue purified by RP-HPLC (CH3CN/H2O/TFA). MS (ESI) m/e 334 (M+H)+, 332 (M−H)−; 1H NMR (500 MHz, CD3OD) δ ppm 2.70 (m, 1H) 3.02 (s, 3H) 3.10 (m, 1H) 3.17 (t, 1H) 3.55 (m, 2H) 3.66 (m, 1H) 3.78 (m, 2H) 3.87 (m, 1H) 4.53 (m, 1H) 4.67 (m, 2H) 7.44 (dd, 2H) 7.48 (m, 3H).

Workup

  1. stirringto stir for 2 hours at room temperature
  2. concentrationconcentrated under reduced pressure
  3. customthe residue was partitioned between ethyl acetate (10 mL) and H2O (5 mL)
  4. extractionThe aqueous layer was extracted with ethyl acetate (2×10 mL)
  5. dry with materialthe combined organic layers were dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customto provide a yellow oil
  9. stirringto stir for 12 hours at room temperature
  10. concentrationThe mixture was concentrated under reduced pressure
  11. customthe residue purified by RP-HPLC (CH3CN/H2O/TFA)

Sources & evidence

ORD record
ord-ccffb3132e584d1caa3b1da42558747e
Source dataset
uspto-grants-2008_03
Patent number
US07348346B2

Reaction notes

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