N-Methyl-4-anisidine → (S)-tert-butyl 3-(3-iodophenyl)-1-((4-methoxyphenyl)(methyl)amino)-1-oxopropan-2-ylcarbamate

HRID 1471624Notes

Reaction equation

HRID 1471624 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([I:20])[CH:15]=1)[C:10]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].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.[CH3:54][O:55][C:56]1[CH:63]=[CH:62][C:59]([NH:60][CH3:61])=[CH:58][CH:57]=1>CN(C=O)C.CCOC(C)=O>[I:20][C:16]1[CH:15]=[C:14]([CH2:13][C@H:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:2])([CH3:3])[CH3:4])[C:10]([N:60]([C:59]2[CH:62]=[CH:63][C:56]([O:55][CH3:54])=[CH:57][CH:58]=2)[CH3:61])=[O:12])[CH:19]=[CH:18][CH:17]=1

Participants

7

Reactant 4

HCID 22250N-Methyl-4-anisidineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 11728885(S)-2-((tert-butoxycarbonyl)amino)-3-(3-iodophenyl)propanoic acid

Product 1

HCID 90289973(S)-tert-butyl 3-(3-iodophenyl)-1-((4-methoxyphenyl)(methyl)amino)-1-oxopropan-2-ylcarbamateYield 94%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

(S)-2-(tert-Butoxycarbonylamino)-3-(3-iodophenyl)propanoic acid (3.8 g, 9.65 mmol), 0-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HATU, 4.4 g, 11.6 mmol) and DIPEA (2.5 ml, 14.5 mmol) were dissolved in DMF (10 ml) and treated with 4-methoxy-N-methylaniline (1.59 g, 11.6 mmol). The mixture was stirred vigorously overnight at room temperature. The mixture was diluted with EtOAc (100 ml) and washed with brine (2×50 ml). The organic layer was dried over Na2SO4, filtered and concentrated. The oily crude product was introduced to a silica gel loading column and purified by column chromatography (15-38% EtOAc/hexanes) to provide the desired product (4.63 g, 9.07 mmol), 94%. MS (m/z) 511 [M+H]+.

Workup

  1. washwashed with brine (2×50 ml)
  2. dry with materialThe organic layer was dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. additionThe oily crude product was introduced to a silica gel loading column
  6. custompurified by column chromatography (15-38% EtOAc/hexanes)

Sources & evidence

ORD record
ord-b66204c6486b414887cffa81090c9b51
Source dataset
uspto-grants-2015_04
Patent number
US09012441B2

Reaction notes

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