Water → 4-(5-chloro-2-fluorophenyl)-2-(3-hydroxyphenyl)-1-(2-methylalanyl)-2,5-dihydro-1H-pyrrole

HRID 2054751Notes

Reaction equation

HRID 2054751 reaction equation
[Si]([O:8][C:9]1[CH:10]=[C:11]([CH:15]2[CH:19]=[C:18]([C:20]3[CH:25]=[C:24]([Cl:26])[CH:23]=[CH:22][C:21]=3[F:27])[CH2:17][N:16]2[C:28](=[O:40])[C:29]([NH:32]C(=O)OC(C)(C)C)([CH3:31])[CH3:30])[CH:12]=[CH:13][CH:14]=1)(C(C)(C)C)(C)C.FC(F)(F)C(O)=O.C(=O)([O-])[O-].[K+].[K+].O>ClCCl.CO>[Cl:26][C:24]1[CH:23]=[CH:22][C:21]([F:27])=[C:20]([C:18]2[CH2:17][N:16]([C:28](=[O:40])[C:29]([CH3:31])([CH3:30])[NH2:32])[CH:15]([C:11]3[CH:12]=[CH:13][CH:14]=[C:9]([OH:8])[CH:10]=3)[CH:19]=2)[CH:25]=1

Participants

7

Reactant 4

HCID 962WaterHCID 6422Trifluoroacetic acidHCID 11430Potassium CarbonateHCID 59656598tert-butyl 2-[2-(3 {[tert-butyl(dimethyl)silyl]oxy}phenyl)-4-(5-chloro-2-fluorophenyl)-2,5-dihydro-1H-pyrrol-1-yl]-1,1-dimethyl-2-oxoethylcarbamate

Product 1

HCID 596566024-(5-chloro-2-fluorophenyl)-2-(3-hydroxyphenyl)-1-(2-methylalanyl)-2,5-dihydro-1H-pyrrole

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of tert-butyl 2-[2-(3{[tert-butyl(dimethyl)silyl]oxy}phenyl)-4-(5-chloro-2-fluorophenyl)-2,5-dihydro-1H-pyrrol-1-yl]-1,1-dimethyl-2-oxoethylcarbamate (3-3, 247 mg, 0.419 mmol, 1 equiv) and trifluoroacetic acid (4 mL) in dichloromethane (10 mL) was stirred under ambient conditions for 1 h. The reaction was concentrated at 23° C. and the residue was partitioned between ethyl acetate and saturated sodium bicarbonate solution. The organic layer was washed with brine, dried over magnesium sulfate and concentrated to yield a yellow gum. A solution of the gum in methanol (5 mL) was treated with potassium carbonate (290 mg, 2.10 mmol, 5.00 equiv) and water (1 mL). The reaction mixture was stirred under ambient conditions for 2 h, then concentrated. The aqueous solution was acidified with aqueous 1 N HCl solution to pH 8 and the mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried over magnesium sulfate and concentrated to provide 4-(5-chloro-2-fluorophenyl)-2-(3-hydroxyphenyl)-1-(2-methylalanyl)-2,5-dihydro-1H-pyrrole (3-4) as a cream-colored solid. 1H NMR (500 MHz, CDCl3) δ 7.30 (dd, 1H, J=6.6, 2.7 Hz), 7.30 (m, 1H), 7.18 (t, 1H, J=7.8 Hz), 7.05 (t, 1H, J=9.2 Hz), 6.83 (br d, 1H, J=7.6 Hz), 6.78 (br s, 1H), 6.70 (dd, 1H, J=8.1, 1.8 Hz), 6.38 (s, 1H), 5.92 (br s, 1H), 5.30 (m, 1H), 5.08 (m, 1H), 1.46 (s, 6H). LRMS m/z (M+H) 375.0 found, 375.0 required.

Workup

  1. concentrationThe reaction was concentrated at 23° C.
  2. customthe residue was partitioned between ethyl acetate and saturated sodium bicarbonate solution
  3. washThe organic layer was washed with brine
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated
  6. customto yield a yellow gum
  7. concentrationconcentrated
  8. extractionthe mixture was extracted with ethyl acetate
  9. washThe organic layer was washed with brine
  10. dry with materialdried over magnesium sulfate
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-0d56b72d49ae4a65b4fbc15f4e56e910
Source dataset
uspto-grants-2008_02
Patent number
US07329762B2

Reaction notes

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