Triethylamine → HCID 57411074, compound

HRID 527713Notes

Reaction equation

HRID 527713 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 188, 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 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 by flash chromatography on silica gel

Sources & evidence

ORD record
ord-df8a817bc8c94cc7b8fccf6f7f560687
Source dataset
uspto-grants-2016_05
Patent number
US09346790B2

Reaction notes

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