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

HRID 1471071Notes

Reaction equation

HRID 1471071 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-e6b46f51e1db4e369b23f696e2cf88a3
Source dataset
uspto-grants-2015_04
Patent number
US09006455B2

Reaction notes

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