p-Anisoyl chloride → HCID 10767748, compound

HRID 1598887Notes

Reaction equation

HRID 1598887 reaction equation
[NH2:1][C@@H:2]([CH:23]([CH3:25])[CH3:24])[C:3]([N:5]1[CH2:9][CH2:8][CH2:7][C@H:6]1[C:10]([NH:12][C@H:13]([C@@H:17]([OH:22])[C:18]([F:21])([F:20])[F:19])[CH:14]([CH3:16])[CH3:15])=[O:11])=[O:4].C(=O)([O-])[O-].[Na+].[Na+].[C:32](Cl)(=[O:41])[C:33]1[CH:38]=[CH:37][C:36]([O:39][CH3:40])=[CH:35][CH:34]=1>C1COCC1>[CH3:40][O:39][C:36]1[CH:37]=[CH:38][C:33]([C:32]([NH:1][C@@H:2]([CH:23]([CH3:25])[CH3:24])[C:3]([N:5]2[CH2:9][CH2:8][CH2:7][C@H:6]2[C:10]([NH:12][C@H:13]([C@@H:17]([OH:22])[C:18]([F:21])([F:19])[F:20])[CH:14]([CH3:16])[CH3:15])=[O:11])=[O:4])=[O:41])=[CH:34][CH:35]=1

Participants

5

Reactant 3

HCID 7477p-Anisoyl chlorideHCID 10340Sodium CarbonateHCID 54010657HCID 54010657, compound

Product 1

HCID 10767748HCID 10767748, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-5 °C

Procedure

Compound C was suspended in THF (350 ml) and powdered sodium carbonate (18.5 g) was added. The mixture was cooled to -5° C. and a solution of anisoyl chloride (11.9 g) in THF (50 ml) was added with stirring. The reaction mixture was stirred an additional 2 hours at 0° C. and then allowed to rise to ambient temperature. The reaction mixture was filtered and the filtrate acidified with 1M hydrochloric acid solution (20 ml) and washed with water. The aqueous layer was extracted with twice with diethyl ether and the combined organic layers washed with 50% saturated sodium bicarbonate solution, brine and dried. Solvent was removed by evaporation to give a colourless foam. The foam was triturated with diethyl ether and the resulting solid was collected by filtration and dried under vacuum at 40° C. for 3 hours to give (S)-1-[(S)-2-(4-methoxybenzamido)-3-methylbutyryl]-N-[(S)-2-methyl-1-((R)-2,2,2-trifluoro-1-hydroxyethyl)propyl]pyrrolidine-2-carboxamide as a white solid, m.p. 168°-170° C.; NMR (300 MHz, d6 -DMSO): 0.82-1.05 (m, 12H), 1.65-2.05 (3m, 5H), 2.05-2.25 (m, 1H), 3.60 (m, 1H), 3.82 (s, 3H+t, 1H), 3.93 (m, 1H), 4.12 (m, 1H), 4.45 (m, 2H), 6.45 (d, 1H), 6.98 (d, 2H), 7.65 (d, 1H), 7.90 (d, 2H), 8.35 (d, 1H).

Workup

  1. stirringThe reaction mixture was stirred an additional 2 hours at 0° C.
  2. customto rise to ambient temperature
  3. filtrationThe reaction mixture was filtered
  4. washwashed with water
  5. extractionThe aqueous layer was extracted with twice with diethyl ether
  6. washthe combined organic layers washed with 50% saturated sodium bicarbonate solution, brine
  7. customdried
  8. customSolvent was removed by evaporation
  9. customto give a colourless foam
  10. customThe foam was triturated with diethyl ether
  11. filtrationthe resulting solid was collected by filtration
  12. customdried under vacuum at 40° C. for 3 hours

Sources & evidence

ORD record
ord-25a4630c25f849cb82855aeab57e0507
Source dataset
uspto-grants-1998_04
Patent number
US05739157

Reaction notes

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