Triethylamine → HCID 69891013, compound

HRID 1837967Notes

Reaction equation

HRID 1837967 reaction equation
[C:1]1([C:7]#[C:8][C:9]([OH:11])=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.S(Cl)(Cl)=O.[CH3:16][O:17][C:18]1[CH:23]=[CH:22][C:21]([C@@H:24]([NH:26][CH2:27][C:28]([O:30][CH2:31][CH3:32])=[O:29])[CH3:25])=[CH:20][CH:19]=1.CCN(CC)CC>CCOCC.C1COCC1.O>[CH3:16][O:17][C:18]1[CH:19]=[CH:20][C:21]([C@@H:24]([N:26]([C:9](=[O:11])[C:8]#[C:7][C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[CH2:27][C:28]([O:30][CH2:31][CH3:32])=[O:29])[CH3:25])=[CH:22][CH:23]=1

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 24386Thionyl ChlorideHCID 69475Phenylpropiolic AcidHCID 69891019HCID 69891019, compound

Product 1

HCID 69891013HCID 69891013, compoundYield 82%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of phenylpropiolic acid (10 g, 68.4 mmol) and thionyl chloride (6 mL, 76.6 mmol) in Et2O (50 mL) was stirred overnight at room temperature. The resulting mixture was concentrated under reduced pressure, then diluted with THF (100 mL). This acid chloride solution was added to a 0° C. solution of ethyl 2-{[(1S)-1-(4-methoxyphenyl)ethyl]amino}acetate (15 g, 63.2 mmol) and Et3N (22 mL, 156 mmol) in THF (250 mL) dropwise over 25 min. The reaction mixture was allowed to warm to room temperature, stirred for 1.5 h, then treated with water and extracted with EtOAc. The organic layer was washed with a 1N HCl solution, water, a saturated NaHCO3 solution and a saturated NaCl solution. The organic layer was dried (Na2SO4) and concentrated under reduced pressure to give ethyl 2-{N-[(1S)-1-(4-methoxyphenyl)ethyl]-3-phenylprop-2-ynoylamino}acetate (18.9 g, 82%) as a slightly yellow oil: TLC (40% EtOAc/hex) Rf 0.40; 1H NMR (CDCl3) δ 1.14-1.33 (m, 3H), 1.66 (d, J=7.0 Hz, 3H), 3.82 (s, 3H), 4.06-4.21 (m, 4H), 5.59 (q, J=7.4 Hz, 0.6H), 6.03 (q, J=7.4 Hz, 0.4H), 6.86-6.93 (m, 2H), 7.25-7.61 (m, 7H); HPLC ES-MS m/z (rel abundance) 388 (MH+, 100%).

Workup

  1. concentrationThe resulting mixture was concentrated under reduced pressure
  2. additiondiluted with THF (100 mL)
  3. temperatureto warm to room temperature
  4. stirringstirred for 1.5 h
  5. extractionextracted with EtOAc
  6. washThe organic layer was washed with a 1N HCl solution, water
  7. dry with materialThe organic layer was dried (Na2SO4)
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-d6325a530b7f4b76bc6105a3e2ced999
Source dataset
uspto-grants-2004_08
Patent number
US06784167B2

Reaction notes

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