Methanamine, N-methoxy-, hydrochloride (1:1) → (S)-tert-butyl 1-(3-fluoro-4-(methoxy(methyl)carbamoyl)phenyl)ethylcarbamate

HRID 1850118Notes

Reaction equation

HRID 1850118 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([C:11]1[CH:19]=[CH:18][C:14]([C:15]([OH:17])=O)=[C:13]([F:20])[CH:12]=1)[CH3:10])=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.[CH3:22][NH:23][O:24][CH3:25].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C.CCOC(C)=O.CCOC(C)=O.CCCCCCC>[F:20][C:13]1[CH:12]=[C:11]([C@@H:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:2])([CH3:3])[CH3:4])[CH3:10])[CH:19]=[CH:18][C:14]=1[C:15](=[O:17])[N:23]([O:24][CH3:25])[CH3:22]

Participants

8

Reactant 4

HCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 86730146(S)-4-(1-(tert-butoxycarbonylamino)ethyl)-2-fluorobenzoic acid

Product 1

HCID 86730148(S)-tert-butyl 1-(3-fluoro-4-(methoxy(methyl)carbamoyl)phenyl)ethylcarbamateYield 92%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolventHCID 21899848Ethylacetate heptaneSolvent

Procedure

A solution of (S)-4-(1-(tert-butoxycarbonylamino)ethyl)-2-fluorobenzoic acid (1.416 g, 5 mmol), N,O-dimethylhydroxylamine hydrochloride (732 mg, 7.5 mmol), HATU (2.85 g, 7.5 mmol) and DIPEA (3.49 mL, 20 mmol) in DMF (25 mL) was stirred at room temperature for 16 h. The reaction mixture was diluted with EtOAc and washed with water. After separation, the aqueous phase was washed with EtOAc (2×75 mL). Combined organics were dried over Na2SO4, filtered and concentrated. Silica gel column chromatography (EtOAc/heptane 12 to 100%) provided (S)-tert-butyl 1-(3-fluoro-4-(methoxy(methyl)carbamoyl)phenyl)ethylcarbamate as a white solid (1.5 g, 92% yield).

Workup

  1. washwashed with water
  2. customAfter separation
  3. washthe aqueous phase was washed with EtOAc (2×75 mL)
  4. dry with materialCombined organics were dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-680e215833a44da087a80fefd35826e6
Source dataset
uspto-grants-2015_02
Patent number
US08957068B2

Reaction notes

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