Triethylamine → (R)-2-(1-(benzyloxy)ethyl)-6-fluoro-3-(3-fluorophenyl)-4H-chromen-4-one

HRID 626295Notes

Reaction equation

HRID 626295 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]([OH:18])=[C:6]([C:8](=[O:17])[CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([F:16])[CH:11]=2)[CH:7]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH2:43]([O:50][C@H:51]([CH3:55])[C:52](O)=O)[C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1.C(N(CC)CC)C>ClCCl>[CH2:43]([O:50][C@@H:51]([C:55]1[O:18][C:5]2[C:6]([C:8](=[O:17])[C:9]=1[C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([F:16])[CH:11]=1)=[CH:7][C:2]([F:1])=[CH:3][CH:4]=2)[CH3:52])[C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 7000104(2R)-2-phenylmethoxypropanoic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 532346871-(5-Fluoro-2-hydroxyphenyl)-2-(3-fluorophenyl)ethanone

Product 1

HCID 117867472(R)-2-(1-(benzyloxy)ethyl)-6-fluoro-3-(3-fluorophenyl)-4H-chromen-4-oneYield 63%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To 1-(5-fluoro-2-hydroxyphenyl)-2-(3-fluorophenyl) ethanone (11 g, 44.31 mmol), in Dichloromethane (110 ml), HATU (33.7 g, 88.63 mmol) and (R)-Benzyloxypropionic acid (9.58 g, 53.17 mmol) were added and stirred for ˜10 min. Triethylamine (67 ml, 478 mmol) was added dropwise and stirred at room temperature (RT) for 24 h. The reaction mixture was quenched with water and extracted with Dichloromethane (2×250 ml). The organic layer was dried with sodium sulphate and concentrated under vacuum. The crude product was purified by column chromatography with ethyl acetate:Petroleum ether to afford the title compound as a off-white solid (10.9 g, 63%). 1H-NMR (δ ppm, CDCl3, 400 MHz): 7.85 (dd, J=8.1, 3.0 Hz, 1H), 7.58 (dd, J=9.1, 4.1 Hz, 1H), 7.47-7.39 (m, 1H), 7.39-7.34 (m, 1H), 7.28-7.20 (m, 3H), 7.20-7.14 (m, 2H), 7.16-7.14 (m, 1H), 6.99-7.89 (m, 2H), 4.50-4.31 (m, 3H), 1.56 (d, J=6.4 Hz, 3H). Mass: 392.9 (M+).

Workup

  1. stirringstirred at room temperature (RT) for 24 h
  2. customThe reaction mixture was quenched with water
  3. extractionextracted with Dichloromethane (2×250 ml)
  4. dry with materialThe organic layer was dried with sodium sulphate
  5. concentrationconcentrated under vacuum
  6. customThe crude product was purified by column chromatography with ethyl acetate

Sources & evidence

ORD record
ord-09a122c5127c47aa9e29aa1549fbec32
Source dataset
uspto-grants-2016_04
Patent number
US09309216B2

Reaction notes

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