Ethyl bromoacetate → HCID 58641285, compound

HRID 1394959Notes

Reaction equation

HRID 1394959 reaction equation
[CH:1]1([CH:4]([OH:26])[C:5]([N:7]2[CH2:11][C:10]([C:12]3[CH:17]=[C:16]([F:18])[CH:15]=[CH:14][C:13]=3[F:19])=[CH:9][C@H:8]2[C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[O:6])[CH2:3][CH2:2]1.[H-].[Na+].Br[CH2:30][C:31]([O:33][CH2:34][CH3:35])=[O:32]>CN(C=O)C>[CH:1]1([C@H:4]([O:26][CH2:30][C:31]([O:33][CH2:34][CH3:35])=[O:32])[C:5]([N:7]2[CH2:11][C:10]([C:12]3[CH:17]=[C:16]([F:18])[CH:15]=[CH:14][C:13]=3[F:19])=[CH:9][C@H:8]2[C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)=[O:6])[CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 7748Ethyl bromoacetateHCID 24758Sodium hydrideHCID 68896988HCID 68896988, compound

Product 1

HCID 58641285HCID 58641285, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
23 °C

Procedure

A solution of (1S)-1-cyclopropyl-2-[(2S)-4-(2,5-difluorophenyl)-2-phenyl-2,5-dihydro-1H-pyrrol-1-yl]-2-oxoethanol (22-9, 150 mg, 0.422 mmol, 1 equiv) in DMP (1 mL) was cooled to 0° C. and treated with a solution of NaH (12 mg, 0.506 mmol, 1.2 eq) in DMF (0.5 ml), then stirred for 10 min. Ethyl bromoacetate (0.078 mL, 0.46 mmol, 1.1 eq) was added to the maroon-colored reaction mixture and the resulting mixture was stirred at 0° C. for 5 min, then warmed to 23° C. and stirred for 30 min. The yellow reaction mixture was partitioned between and water (65 mL) and EtOAc (2×60 mL) and the combined organic layers were dried over sodium sulfate and concentrated. The residue was purified by reverse-phase liquid chromatography (acetonitrile/H2O with 0.1% TEA present) to afford ethyl ({(1S)-1-cyclopropyl-2-[(2S)-4-(2,5-difluorophenyl)-2-phenyl-2,5-dihydro-1H-pyrrol-1-yl]-2-oxoethyl}oxy)acetate (40-1) as a light yellow oil. 1H NMR (300, CDCl3) major rotamer: δ 7.22-7.39 (m, 5H), 6.93-7.12 (m, 3H), 6.42 (br s), 5.87 (d, 1H, J=2.4 Hz), 4.93 (br s, 2H), 4.29 (m, 2H), 3.92 (d, 1H, J=7.6 Hz), 3.66 (d, 1H, J=8.8 Hz), 3.41 (d, 1H, J=8.8 Hz), 1.18 (t, 3H, J=7.3 Hz), 0.61 (m, 4H). LRMS m/z (M+H) 442.4 found, 442.5 required.

Workup

  1. stirringthe resulting mixture was stirred at 0° C. for 5 min
  2. stirringstirred for 30 min
  3. customThe yellow reaction mixture was partitioned between and water (65 mL) and EtOAc (2×60 mL)
  4. dry with materialthe combined organic layers were dried over sodium sulfate
  5. concentrationconcentrated
  6. customThe residue was purified by reverse-phase liquid chromatography (acetonitrile/H2O with 0.1% TEA present)

Sources & evidence

ORD record
ord-15d82a240a8742d1a679592e8c6200a0
Source dataset
uspto-grants-2008_03
Patent number
US07348440B2

Reaction notes

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