Ethylene Glycol → HCID 15950258, compound

HRID 1394955Notes

Reaction equation

HRID 1394955 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[C:9]1[CH2:13][N:12]([C:14]([C@@H:16]([NH:21][C:22](=[O:33])[O:23][C:24]2C=CC([N+]([O-])=O)=C[CH:25]=2)[C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[C@H:11]([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[CH:10]=1.C(O)C[OH:42]>>[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[C:9]1[CH2:13][N:12]([C:14]([C@@H:16]([NH:21][C:22](=[O:33])[O:23][CH2:24][CH2:25][OH:42])[C:17]([CH3:19])([CH3:20])[CH3:18])=[O:15])[C@H:11]([C:34]2[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=2)[CH:10]=1

Participants

3

Reactant 2

HCID 174Ethylene GlycolHCID 59656614HCID 59656614, compound

Product 1

HCID 15950258HCID 15950258, compound

Conditions

Temperature
100 °C

Procedure

A mixture of 4-nitrophenyl (1S)-1-{[(2S)-4-(2,5-difluorophenyl)-2-phenyl-2,5-dihydro-1H-pyrrol-1-yl]carbonyl}-2,2-dimethylpropylcarbamate (36-1, 500 mg, 0.93 mmol, 1.0 equiv) and ethylene glycol (3 mL, excess) was heated at 100° C. for 1 h. The reaction mixture was cooled and partitioned between ethyl acetate and water. The organic layer was washed with brine, dried over magnesium sulfate and concentrated. The residue was purified by flash chromatography on silica gel. Elution with 20% ethyl acetate/dichloromethane to 50% ethyl acetate/dichloromethane gave 2-hydroxyethyl (1S)-1-{[(2S)-4-(2,5-difluorophenyl)-2-phenyl-2,5-dihydro-1H-pyrrol-1-yl]carbonyl}-2,2-dimethylpropylcarbamate (36-2) as a colorless foam. 1H NMR (500 MD, CDCl3) major rotamer: δ 7.38-7.21 (m, 5H), 7.11-6.94 (m, 3H), 6.40 (s, 1H), 5.92 (m, 1H), 5.51 (m, 1H), 5.07 (d, 1H, J=13 Hz), 4.91 (m, 1H), 4.37 (d, 1H, J=10 Hz), 4.20 (m, 2H), 3.81 (t, 2H, J=4.5 Hz), 3.64 (t, 1H, J=4 Hz),) 0.91 (s, 9H). LRMS m/z (M+H) 459.3 found, 459.2 required.

Workup

  1. temperatureThe reaction mixture was cooled
  2. custompartitioned between ethyl acetate and water
  3. washThe organic layer was washed with brine
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated
  6. customThe residue was purified by flash chromatography on silica gel
  7. washElution with 20% ethyl acetate/dichloromethane to 50% ethyl acetate/dichloromethane

Sources & evidence

ORD record
ord-7da644723a8b498482b0bae0fd7ca09f
Source dataset
uspto-grants-2008_03
Patent number
US07348440B2

Reaction notes

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