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Trifluoroacetic acid → (2R)-2-amino-N-[6-(7-methylspiro[2H-benzofuran-3,1'-cyclopropane]-4-yl)oxy-3-pyridyl]butanamide

HRID 527621
Notes
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Reaction equation

HRID 527621 reaction equation
[CH3:1][C:2]1[C:7]2[O:8][CH2:9][C:10]3([CH2:12][CH2:11]3)[C:6]=2[C:5]([O:13][C:14]2[N:19]=[CH:18][C:17]([NH:20][C:21]([C@H:23]([NH:26]C(=O)OC(C)(C)C)[CH2:24][CH3:25])=[O:22])=[CH:16][CH:15]=2)=[CH:4][CH:3]=1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH2:26][C@H:23]([CH2:24][CH3:25])[C:21]([NH:20][C:17]1[CH:18]=[N:19][C:14]([O:13][C:5]2[C:6]3[C:10]4([CH2:9][O:8][C:7]=3[C:2]([CH3:1])=[CH:3][CH:4]=2)[CH2:12][CH2:11]4)=[CH:15][CH:16]=1)=[O:22]
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86698449tert-butyl N-[(1R)-1-[[6-(7-methylspiro[2H-benzofuran-3,1'-cyclopropane]-4-yl)oxy-3-pyridyl]carbamoyl]propyl]carbamate2×

Product 1

HCID 67960014(2R)-2-amino-N-[6-(7-methylspiro[2H-benzofuran-3,1'-cyclopropane]-4-yl)oxy-3-pyridyl]butanamideYield 95.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl N-[(1R)-1-[[6-(7-methylspiro[2H-benzofuran-3,1′-cyclopropane]-4-yl)oxy-3-pyridyl]carbamoyl]propyl]carbamate (Intermediate 159, 55 mg) in dry DCM (3 ml) at 0° C. TFA (1 ml) was slowly added and the reaction mixture was stirred for 3 hours at the same temperature. The solvent and the excess of TFA were removed under reduced pressure and the residue was diluted with DCM (10 ml) and an aqueous saturated solution NaHCO3 was added while the pH was allowed to reach ˜8. Two phases were separated and the organic layer was dried (Na2SO4), filtered and evaporated affording the title compound (41 mg) as white solid.

Workup

  1. customat 0° C
  2. customThe solvent and the excess of TFA were removed under reduced pressure
  3. additionthe residue was diluted with DCM (10 ml)
  4. additionan aqueous saturated solution NaHCO3 was added while the pH
  5. customTwo phases were separated
  6. dry with materialthe organic layer was dried (Na2SO4)
  7. filtrationfiltered
  8. customevaporated

Sources & evidence

ORD record
ord-20850cb1f4294b5e8cdaa0009af86f74
Source dataset
uspto-grants-2016_05
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US09346790B2

Reaction notes

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