3-(Trifluoromethoxy)aniline → HCID 52716430, compound

HRID 1527546Notes

Reaction equation

HRID 1527546 reaction equation
[C:1]([N:8]1[CH2:15][CH2:14][CH2:13][C@H:9]1[C:10]([OH:12])=O)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[F:16][C:17]([F:27])([F:26])[O:18][C:19]1[CH:20]=[C:21]([CH:23]=[CH:24][CH:25]=1)[NH2:22].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C>[C:4]([O:3][C:1]([N:8]1[CH2:15][CH2:14][CH2:13][C@H:9]1[C:10](=[O:12])[NH:22][C:21]1[CH:23]=[CH:24][CH:25]=[C:19]([O:18][C:17]([F:16])([F:26])[F:27])[CH:20]=1)=[O:2])([CH3:5])([CH3:6])[CH3:7]

Participants

6

Reactant 4

HCID 737533-(Trifluoromethoxy)anilineHCID 81531DiisopropylethylamineHCID 850831,2-Pyrrolidinedicarboxylic acid, 1-(1,1-dimethylethyl) ester, (2S)-HCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

Product 1

HCID 52716430HCID 52716430, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a mixture of Boc-L-proline (5 g, 23.23 mmol), 3-(trifluoromethoxy)aniline (3.73 mL, 27.88 mmol) and HBTU (13.2 g, 34.8 mmol) in DMF (60 mL) was added DIPEA (7.95 mL, 46.5 mmol) and the resulting yellow solution was stirred at RT under nitrogen. The solvent was concentrated under vacuum and the residue dissolved in EtOAc and washed with HCl 1N. The combined organic layers were neutralized by addition of an aqueous saturated solution of NaHCO3. The layers were separated and the aqueous one back-extracted twice with CH2Cl2. The combined organic extracts were dried (Na2SO4), filtered and concentrated. The crude residue was purified by flash column chromatography on silica gel (c-hexane/EtOAc 3:1 to 2:1) to give the desired compound. TLC, Rf (c-hexane/EtOAc 1:1)=0.57; MS (LC/MS): 397.1 [M+Na]+, 275.2 [MH−Boc]+, 373.3 [M−H]−; tR (HPLC conditions a) 3.81 min.

Workup

  1. concentrationThe solvent was concentrated under vacuum
  2. dissolutionthe residue dissolved in EtOAc
  3. washwashed with HCl 1N
  4. additionThe combined organic layers were neutralized by addition of an aqueous saturated solution of NaHCO3
  5. customThe layers were separated
  6. extractionthe aqueous one back-extracted twice with CH2Cl2
  7. dry with materialThe combined organic extracts were dried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude residue was purified by flash column chromatography on silica gel (c-hexane/EtOAc 3:1 to 2:1)

Sources & evidence

ORD record
ord-a82a945a50c74e019c8f867766ddde50
Source dataset
uspto-grants-2015_07
Patent number
US09085555B2

Reaction notes

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