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Triphosgene → QZ8Etv7qyu

HRID 527712
Notes
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Reaction equation

HRID 527712 reaction equation
[NH2:1][C@H:2]([CH2:25][CH3:26])[C:3]([NH:5][C:6]1[CH:7]=[N:8][C:9]([O:12][C:13]2[C:18]3[C:19]4([CH2:22][O:23][C:17]=3[C:16]([CH3:24])=[CH:15][CH:14]=2)[CH2:21][CH2:20]4)=[CH:10][CH:11]=1)=[O:4].Cl[C:28](Cl)([O:30]C(=O)OC(Cl)(Cl)Cl)Cl>C(Cl)Cl>[CH2:25]([C@H:2]1[NH:1][C:28](=[O:30])[N:5]([C:6]2[CH:7]=[N:8][C:9]([O:12][C:13]3[C:18]4[C:19]5([CH2:22][O:23][C:17]=4[C:16]([CH3:24])=[CH:15][CH:14]=3)[CH2:21][CH2:20]5)=[CH:10][CH:11]=2)[C:3]1=[O:4])[CH3:26]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

4

Reactant 2

HCID 94429TriphosgeneHCID 67960014(2R)-2-amino-N-[6-(7-methylspiro[2H-benzofuran-3,1'-cyclopropane]-4-yl)oxy-3-pyridyl]butanamide2×

Product 1

HCID 67959994QZ8Etv7qyuYield 72.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of (2R)-2-amino-N-[6-(7-methylspiro[2H-benzofuran-3,1′-cyclopropane]-4-yl)oxy-3-pyridyl]butanamide (Intermediate 160, 40 mg, 0.11 mmol) in dry DCM (5 ml) TEA (0.042 ml, 0.3 mmol) was added and the reaction mixture was cooled to 0° C. A solution of triphosgene (23.7 mg, 0.08 mmol) in dry DCM (3 ml) was slowly added and the reaction mixture was stirred for 15 minutes at the same temperature. The reaction was quenched with water (10 ml) and two phases were separated. The organic layer was dried (Na2SO4), filtered and evaporated and the residue was purified by flash chromatography (Biotage system) on silica gel using a 10 g SNAP column and cyclohexane/ethyl acetate 75:25 to cyclohexane/ethyl acetate 25:75 as eluents affording the title compound (22 mg) as a white solid.

Workup

  1. customThe reaction was quenched with water (10 ml) and two phases
  2. customwere separated
  3. dry with materialThe organic layer was dried (Na2SO4)
  4. filtrationfiltered
  5. customevaporated
  6. customthe residue was purified by flash chromatography (Biotage system) on silica gel using a 10 g SNAP column and cyclohexane/ethyl acetate 75:25 to cyclohexane/ethyl acetate 25:75 as eluents

Sources & evidence

ORD record
ord-2a492352328b47f38c1a3ff93e4a0651
Source dataset
uspto-grants-2016_05
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US09346790B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes