3-(Trifluoromethyl)aniline → HCID 52881078, compound

HRID 1160108Notes

Reaction equation

HRID 1160108 reaction equation
[C:1]([N:8]([CH2:10][C:11]([OH:13])=O)[CH3:9])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[F:47][C:48]([F:57])([F:56])[C:49]1[CH:50]=[C:51]([CH:53]=[CH:54][CH:55]=1)[NH2:52]>CCOC(C)=O.CN(C=O)C>[C:4]([O:3][C:1](=[O:2])[N:8]([CH3:9])[CH2:10][C:11](=[O:13])[NH:52][C:51]1[CH:53]=[CH:54][CH:55]=[C:49]([C:48]([F:47])([F:56])[F:57])[CH:50]=1)([CH3:5])([CH3:6])[CH3:7]

Participants

7

Reactant 4

HCID 73753-(Trifluoromethyl)anilineHCID 81531DiisopropylethylamineHCID 83692Glycine, N-[(1,1-dimethylethoxy)carbonyl]-N-methyl-HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

Product 1

HCID 52881078HCID 52881078, compoundYield 64.8%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a 25 mL round bottomed flask was added Boc-sarcosine (378 mg, 2.0 mmol, 1.0 eq.), DMF (10.0 mL), DIEA (0.35 mL, 2.0 mmol, 2.0 eq.), HATU (836 mg, 2.2 mmol, 2.2 eq.) and 3-trifluoromethylaniline (0.4 mL, 3.0 mmol, 1.5 eq.). The reaction was allowed to stir at RT overnight before quenching with H2O (20 mL) and EtOAc (100 mL). The organic layer was then washed 2× with 10% LiCl, washed with brine, dried with Na2SO4, and concentrated to give an oil. Further drying on high vacuum then gave a solid. Column chromatography on silica gel with 60:40 EtOAc:Hex gave methyl-[(3-trifluoromethyl-phenylcarbamoyl)-methyl]-carbamic acid tert-butyl ester (431 mg, 64%). LC/MSD (HP Series 1100 MSD): Expected MW: 332, Observed M−H: 331, Retention time: 1.6 min. 1H-NMR (d6-DMSO): 10.35 (d, 1H), 8.10 (d, 1H), 7.75 (dd, 1H), 7.55 (t, 1H), 7.40 (d, 1H), 4.00 (d, 2H), 2.88 (d, 3H), 1.40 (d, 9H) ppm.

Workup

  1. custombefore quenching with H2O (20 mL) and EtOAc (100 mL)
  2. washThe organic layer was then washed 2× with 10% LiCl
  3. washwashed with brine
  4. dry with materialdried with Na2SO4
  5. concentrationconcentrated
  6. customto give an oil
  7. customFurther drying on high vacuum
  8. customthen gave a solid

Sources & evidence

ORD record
ord-e2f34b2e53f14041bb1226bcd9703d55
Source dataset
uspto-grants-2010_10
Patent number
US07816353B2

Reaction notes

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