3-(Trifluoromethoxy)aniline → HCID 68283302, compound

HRID 1527316Notes

Reaction equation

HRID 1527316 reaction equation
[C:1]([N:8]1[CH2:15][C:14](=[CH2:16])[CH2:13][C@H:9]1[C:10]([OH:12])=O)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[F:17][C:18]([F:28])([F:27])[O:19][C:20]1[CH:21]=[C:22]([CH:24]=[CH:25][CH:26]=1)[NH2:23].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C>C(Cl)Cl>[C:4]([O:3][C:1]([N:8]1[CH2:15][C:14](=[CH2:16])[CH2:13][C@H:9]1[C:10](=[O:12])[NH:23][C:22]1[CH:24]=[CH:25][CH:26]=[C:20]([O:19][C:18]([F:17])([F:27])[F:28])[CH:21]=1)=[O:2])([CH3:5])([CH3:6])[CH3:7]

Participants

6

Reactant 4

HCID 737533-(Trifluoromethoxy)anilineHCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 21727417(2S)-1-((tert-butoxy)carbonyl)-4-methylidenepyrrolidine-2-carboxylic acid

Product 1

HCID 68283302HCID 68283302, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a suspension of N-Boc-4-methylene-L-proline (1 g, 4.4 mmol) in CH2Cl2 (40 mL) was added 3-(trifluoromethoxy)aniline (0.71 mL, 5.28 mmol), HBTU (1.14 g, 6.6 mmol) and diisopropylethylamine (1.51 mL, 8.8 mmol). The reaction mixture was stirred at RT for 2 days. The mixture was successively washed with 30 mL of a saturated aqueous NaHCO3 solution and an HCl 1M solution. The organic layers were dried (phase separator) and concentrated under vacuum. The crude residue was purified by flash column chromatography on silica gel (eluent: c-hexane/EtOAc:65/35) to give the title compound. TLC, Rf (c-hexane/EtOAc: 1:1)=0.55; MS (LC/MS): 287.0 [M-Boc]+, 385.0 [M−H]−.

Workup

  1. washThe mixture was successively washed with 30 mL of a saturated aqueous NaHCO3 solution
  2. customThe organic layers were dried (phase separator)
  3. concentrationconcentrated under vacuum
  4. customThe crude residue was purified by flash column chromatography on silica gel (eluent: c-hexane/EtOAc:65/35)

Sources & evidence

ORD record
ord-7fa72203b64e4938ae851a8b0554ed72
Source dataset
uspto-grants-2015_07
Patent number
US09085555B2

Reaction notes

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