Water → ethyl (R)-2-tert-butoxycarbonylamino-5-(2,5-difluorophenyl)-5-oxopentanoate

HRID 553932Notes

Reaction equation

HRID 553932 reaction equation
[Mg].[CH3:2][CH2:3][O:4][C:5]([C@H:7]1[CH2:11][CH2:10][C:9](=[O:12])[N:8]1[C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])=[O:6].O.Br[C:22]1[CH:27]=[C:26]([F:28])[CH:25]=[CH:24][C:23]=1[F:29]>O1CCCC1>[C:16]([O:15][C:13]([NH:8][C@H:7]([CH2:11][CH2:10][C:9]([C:22]1[CH:27]=[C:26]([F:28])[CH:25]=[CH:24][C:23]=1[F:29])=[O:12])[C:5]([O:4][CH2:3][CH3:2])=[O:6])=[O:14])([CH3:19])([CH3:18])[CH3:17]

Participants

6

Reactant 4

HCID 962WaterHCID 678622-Bromo-1,4-difluorobenzeneHCID 8208851-Boc-D-Pyroglutamic acid ethyl esterHCID 5462224Magnesium

Product 1

HCID 67464850ethyl (R)-2-tert-butoxycarbonylamino-5-(2,5-difluorophenyl)-5-oxopentanoate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a suspension of magnesium (0.569 g) in tetrahydrofuran (20 mL), 1-bromo-2,5-difluorobenzene (2.64 mL) was added dropwise at 55° C. over 15 minutes, and the reaction solution was stirred at room temperature for one hour. This solution was added dropwise to a solution of (R)-5-oxopyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-ethyl ester (5.0 g) in tetrahydrofuran (25 mL) at −40° C. over 20 minutes, and the reaction solution was stirred at −40° C. to 0° C. for one hour. Water was added to the solution in small portions at 0° C., followed by extraction with ethyl acetate. The extract was washed with brine, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (heptane-ethyl acetate system) to obtain 5.7 g of the title compound as a colorless oil. The property values of the compound are as follows.

Workup

  1. additionwas added dropwise at 55° C. over 15 minutes
  2. stirringthe reaction solution was stirred at −40° C. to 0° C. for one hour
  3. extractionfollowed by extraction with ethyl acetate
  4. washThe extract was washed with brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel column chromatography (heptane-ethyl acetate system)

Sources & evidence

ORD record
ord-2c57a50b9eda4907812ab640ab06989e
Source dataset
uspto-grants-2011_11
Patent number
US08048878B2

Reaction notes

Loading…