1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → (S)-1-Phenylethyl 2-(2-fluorophenyl)acetate

HRID 1919193Notes

Reaction equation

HRID 1919193 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][C:9]([OH:11])=[O:10].[C:12]1([C@@H:18](O)[CH3:19])[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.CCN=C=NCCCN(C)C>CN(C1C=CN=CC=1)C.C(Cl)Cl>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][C:9]([O:11][C@H:18]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[CH3:19])=[O:10]

Participants

6

Reactant 3

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 67979Benzeneacetic acid, 2-fluoro-HCID 4431351-Phenylethanol, (S)-

Product 1

HCID 66648658(S)-1-Phenylethyl 2-(2-fluorophenyl)acetateYield 92%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

A mixture of 2-fluorophenylacetic acid (5.45 g, 35.4 mmol), (S)-1-phenylethanol (5.62 g, 46.0 mmol), EDCI (8.82 g, 46.0 mmol) and DMAP (0.561 g, 4.60 mmol) in CH2Cl2 (100 mL) was stirred at room temperature for 12 hours. The solvent was then concentrated and the residue partitioned with H2O-ethyl acetate. The phases were separated and the aqueous layer back-extracted with ethyl acetate (2×). The combined organic phases were washed (H2O, brine), dried (Na2SO4), filtered, and concentrated in vacuo. The residue was purified by silica gel chromatography (BIOTAGE®/0-20% ethyl acetate-hexane) to provide the title compound as a colorless oil (8.38 g, 92%). 1H NMR (400 MHz, CD3OD) δ 7.32-7.23 (m, 7H), 7.10-7.04 (m, 2), 5.85 (q, J=6.5 Hz, 1H), 3.71 (s, 2H), 1.48 (d, J=6.5 Hz, 3H).

Workup

  1. concentrationThe solvent was then concentrated
  2. customthe residue partitioned with H2O-ethyl acetate
  3. customThe phases were separated
  4. extractionthe aqueous layer back-extracted with ethyl acetate (2×)
  5. washThe combined organic phases were washed (H2O, brine)
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by silica gel chromatography (BIOTAGE®/0-20% ethyl acetate-hexane)

Sources & evidence

ORD record
ord-00d519be577c4ed7a4f54f310593bada
Source dataset
uspto-grants-2013_12
Patent number
US08618153B2

Reaction notes

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