Triethylamine → HCID 53241496, compound

HRID 1505397Notes

Reaction equation

HRID 1505397 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([O:9][C:10]2[CH:15]=[CH:14][C:13]([NH:16][C:17](=[O:21])[C@@H:18]([CH3:20])[NH2:19])=[CH:12][CH:11]=2)[CH:6]=[CH:7][CH:8]=1.C(N(CC)CC)C.Cl[C:30](Cl)([O:32]C(=O)OC(Cl)(Cl)Cl)Cl>C(OCC)(=O)C.CN(C1C=CN=CC=1)C>[CH3:20][C@H:18]1[NH:19][C:30](=[O:32])[N:16]([C:13]2[CH:14]=[CH:15][C:10]([O:9][C:5]3[CH:6]=[CH:7][CH:8]=[C:3]([O:2][CH3:1])[CH:4]=3)=[CH:11][CH:12]=2)[C:17]1=[O:21]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 94429TriphosgeneHCID 39387374HCID 39387374, compound2×

Product 1

HCID 53241496HCID 53241496, compoundYield 66.9%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of N1-(4-{[3-(methyloxy)phenyl]oxy}phenyl)-D-alaninamide (Intermediate 2, 315 mg) and triethyl amine (0.307 mL, 2.200 mmol) in dry ethyl acetate (5 mL), triphosgene (163 mg, 0.550 mmol) was added and the reaction mixture was stirred for 5 minutes. DMAP (67.2 mg, 0.550 mmol) was then added and the reaction mixture was stirred for further 10 minutes. The reaction was quenched with a saturated solution of sodium carbonate (5 mL), diluted with water (10 mL) and extracted with ethyl acetate (3 times 20 mL). The organic layer was dried over sodium sulphate, filtered and evaporated. The residue was purified by silica gel chromatography (Biotage system, 10 g SNAP column) eluting with a gradient cyclohexane/ethyl acetate from 100/0 to 60/40 to afford the title compound as a white solid (115 mg).

Workup

  1. stirringthe reaction mixture was stirred for further 10 minutes
  2. customThe reaction was quenched with a saturated solution of sodium carbonate (5 mL)
  3. additiondiluted with water (10 mL)
  4. extractionextracted with ethyl acetate (3 times 20 mL)
  5. dry with materialThe organic layer was dried over sodium sulphate
  6. filtrationfiltered
  7. customevaporated
  8. customThe residue was purified by silica gel chromatography (Biotage system, 10 g SNAP column)
  9. washeluting with a gradient cyclohexane/ethyl acetate from 100/0 to 60/40

Sources & evidence

ORD record
ord-98ee54f2e6674ba5828ff6f52b574c4b
Source dataset
uspto-grants-2015_12
Patent number
US09216967B2

Reaction notes

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