Hydrochloric Acid → HCID 14774463, compound

HRID 539008Notes

Reaction equation

HRID 539008 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH:13]([CH3:15])[CH3:14])[C:10]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1C=CC2N(O)N=NC=2C=1.O.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:60][O:61][C:62]1[CH:69]=[CH:68][C:65]([CH2:66][NH2:67])=[CH:64][CH:63]=1.Cl>C1COCC1>[CH3:60][O:61][C:62]1[CH:69]=[CH:68][C:65]([CH2:66][NH:67][C:10](=[O:12])[C@@H:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:2])([CH3:3])[CH3:4])[CH:13]([CH3:15])[CH3:14])=[CH:64][CH:63]=1

Participants

8

Reactant 6

HCID 313Hydrochloric AcidHCID 754524-MethoxybenzylamineHCID 81531DiisopropylethylamineHCID 83693Boc-L-ValineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 27960291-Hydroxybenzotriazole hydrate

Product 1

HCID 14774463HCID 14774463, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A solution of (S)-2-(tert-butoxycarbonylamino)-3-methylbutanoic acid (2.50 g, 11.5 mmol), HOBT-H2O (1.76 g, 11.5 mmol) and DIEA (6.01 mL, 34.5 mmol) in THF (50 mL) was cooled to 0° C. HBTU (3.23 g, 13.8 mmol) was added and the mixture stirred at 0° C. for 30 minutes prior to addition of 4-methoxy-benzylamine (2.25 mL, 17.3 mmol). The reaction mixture was allowed to warm slowly to ambient temperature while stirring over 48 hours. The reaction mixture was poured into 10% HCl and extracted with ethyl acetate. The combined organic extracts were dried over sodium sulfate, filtered and concentrated. Purification of the crude material by column chromatography, eluting with 1.5-3% MeOH/dichloromethane afforded (S)-tert-butyl 1-(4-methoxybenzylamino)-3-methyl-1-oxobutan-2-ylcarbamate as a light yellow solid, 2.70 g (70%).

Workup

  1. temperatureto warm slowly to ambient temperature
  2. stirringwhile stirring over 48 hours
  3. extractionextracted with ethyl acetate
  4. dry with materialThe combined organic extracts were dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification of the crude material by column chromatography
  8. washeluting with 1.5-3% MeOH/dichloromethane

Sources & evidence

ORD record
ord-9a2759ef10ac448db9f490d55931e2cf
Source dataset
uspto-grants-2014_10
Patent number
US08865726B2

Reaction notes

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