4-Methylmorpholine → 2-[3-(4-Bromophenoxy)-2-tert-butoxycarbonylamino-propionylamino]-3-methyl-butyric acid methyl ester

HRID 2197270Notes

Reaction equation

HRID 2197270 reaction equation
[Br:1][C:2]1[CH:21]=[CH:20][C:5]([O:6][CH2:7][CH:8]([NH:12][C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[C:9]([OH:11])=O)=[CH:4][CH:3]=1.CN1CCOCC1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.Cl.[NH2:52][C@H:53]([CH:58]([CH3:60])[CH3:59])[C:54]([O:56][CH3:57])=[O:55]>CN(C=O)C>[CH3:57][O:56][C:54](=[O:55])[CH:53]([NH:52][C:9](=[O:11])[CH:8]([NH:12][C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:7][O:6][C:5]1[CH:4]=[CH:3][C:2]([Br:1])=[CH:21][CH:20]=1)[CH:58]([CH3:60])[CH3:59]

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 11984198Methyl D-valinate hydrochlorideHCID 66660912HCID 66660912, compound2×

Product 1

HCID 666609032-[3-(4-Bromophenoxy)-2-tert-butoxycarbonylamino-propionylamino]-3-methyl-butyric acid methyl esterYield 84%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
-15 °C

Procedure

A solution of the compound obtained in step e above (22e) (816 mg, 2.27 mmol), NMM (0.55 mL, 4.922 mmol) and HOBt (521 mg, 3.864 mmol) in DMF (10 mL) was stirred at 0° C. for 10 minutes, then the reaction was cooled to −15° C., and EDCl (478 mg, 2.497 mmol) was added. The reaction was stirred for 30 minutes at −15° C. and then allowed to warm to room temperature, (R)-methyl 2-amino-3-methylbutanoate hydrochloride (417 mg, 2.497 mmol) was added. After being stirred overnight, the reaction mixture was concentrated under vacuum; the residue was diluted with EtOAc and washed with brine. The combined organic layers were dried and concentrated; the residue was purified by silica gel column chromatography to give the title compound as colourless oil (900 mg, 84%).

Workup

  1. temperatureto warm to room temperature
  2. stirringAfter being stirred overnight
  3. concentrationthe reaction mixture was concentrated under vacuum
  4. additionthe residue was diluted with EtOAc
  5. washwashed with brine
  6. customThe combined organic layers were dried
  7. concentrationconcentrated
  8. customthe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-51fdda5d35b14343bb07487f0c578983
Source dataset
uspto-grants-2012_12
Patent number
US08338471B2

Reaction notes

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