Triethylamine → HCID 57411074, compound

HRID 1484664Notes

Reaction equation

HRID 1484664 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]([CH3:23])([CH3:22])[CH2:20][O:21][C:17]=3[C:16]([CH3:24])=[CH:15][CH:14]=2)=[CH:10][CH:11]=1)=[O:4].C(N(CC)CC)C.Cl[C:35](Cl)([O:37]C(=O)OC(Cl)(Cl)Cl)Cl.C([O-])(O)=O.[Na+]>C(OCC)(=O)C>[CH2:25]([C@H:2]1[NH:1][C:35](=[O:37])[N:5]([C:6]2[CH:7]=[N:8][C:9]([O:12][C:13]3[C:18]4[C:19]([CH3:22])([CH3:23])[CH2:20][O:21][C:17]=4[C:16]([CH3:24])=[CH:15][CH:14]=3)=[CH:10][CH:11]=2)[C:3]1=[O:4])[CH3:26]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 94429TriphosgeneHCID 516892Sodium BicarbonateHCID 86698456HCID 86698456, compound2×

Product 1

HCID 57411074HCID 57411074, compoundYield 128%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
0 °C

Procedure

(2R)-2-amino-N-{6-[(3,3,7-trimethyl-2,3-dihydro-1-benzofuran-4-yl)oxy]-3-pyridinyl}butanamide (Intermediate 31, 300 mg, 0.84 mmol) was dissolved in ethyl acetate (6 mL). Triethylamine (0.47 ml, 3.36 mmol) was added and the reaction mixture was cooled to 0° C. A solution of triphosgene (100 mg, 0.34 mmol) in ethyl acetate (6 mL) was slowly added. At the end of addition the mixture was treated with an aqueous saturated solution of NaHCO3 and two phases were separated. The organic layer was washed with brine, dried over Na2SO4 and evaporated to dryness to obtain a waxy solid. The residue was purified purified by flash chromatography on silica gel using cyclohexane/ethyl acetate 70:30 to cyclohexane/ethyl acetate 50:50 as eluents affording the title compound (166 mg) as a white foam.

Workup

  1. additionAt the end of addition the mixture
  2. customwere separated
  3. washThe organic layer was washed with brine
  4. dry with materialdried over Na2SO4
  5. customevaporated to dryness
  6. customto obtain a waxy solid
  7. customThe residue was purified
  8. custompurified by flash chromatography on silica gel

Sources & evidence

ORD record
ord-2fa53bffe9fa4c089a7e303f7b4c7c65
Source dataset
uspto-grants-2016_08
Patent number
US09422272B2

Reaction notes

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