Diisopropylamine → (r)-5-[2-(4-Fluorophenyl)-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1h-pyrrol-1-yl]-3-hydroxy-1-pentanoic acid, (s)-2-hydroxy-1,2,2-triphenylethyl ester

HRID 33602

Reaction equation

HRID 33602 reaction equation
[CH3:1][C:2]([O:4][C@H:5]([C:12]([OH:25])([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)=[O:3].[Li+].CC([N-]C(C)C)C.C(NC(C)C)(C)C.[F:41][C:42]1[CH:47]=[CH:46][C:45]([C:48]2[N:52]([CH2:53][CH2:54][CH:55]=[O:56])[C:51]([CH:57]([CH3:59])[CH3:58])=[C:50]([C:60]([NH:62][C:63]3[CH:68]=[CH:67][CH:66]=[CH:65][CH:64]=3)=[O:61])[C:49]=2[C:69]2[CH:74]=[CH:73][CH:72]=[CH:71][CH:70]=2)=[CH:44][CH:43]=1>C1COCC1.O.CC(O)=O>[F:41][C:42]1[CH:43]=[CH:44][C:45]([C:48]2[N:52]([CH2:53][CH2:54][C@@H:55]([OH:56])[CH2:1][C:2]([O:4][C@@H:5]([C:6]3[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=3)[C:12]([OH:25])([C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=3)[C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)=[O:3])[C:51]([CH:57]([CH3:59])[CH3:58])=[C:50]([C:60]([NH:62][C:63]3[CH:64]=[CH:65][CH:66]=[CH:67][CH:68]=3)=[O:61])[C:49]=2[C:69]2[CH:74]=[CH:73][CH:72]=[CH:71][CH:70]=2)=[CH:46][CH:47]=1

Participants

8

Reactant 4

HCID 7912DiisopropylamineHCID 7360481,2-Ethanediol, 1,1,2-triphenyl-, 2-acetate, (2S)-HCID 2724682Lithium diisopropylamideHCID 113055725-(4-Fluorophenyl)-2-(1-methylethyl)-1-(3-oxopropyl)-N,4-diphenyl-1H-pyrrole-3-carboxamide

Product 1

HCID 11193615(r)-5-[2-(4-Fluorophenyl)-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1h-pyrrol-1-yl]-3-hydroxy-1-pentanoic acid, (s)-2-hydroxy-1,2,2-triphenylethyl ester

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

To a suspension of S-(−)-2-Hydroxy-1,2,2-triphenylethyl acetate (40.2 g) in 300 mL anhydrous THF at −10 to 0° C. was added a solution of LDA prepared by reaction of diisopropylamine (46.5 mL) with 2.5 M n-BuLi/hexanes (97 mL) in 300 mL anhydrous THF at −5 to 0° C. After stirring at 0° C. for 30 min the mixture was cooled to −78° C. Then, a solution of 5-(4-fluorophenyl)-2-(1-methylethyl)-1-(3-oxopropyl)-N,4-diphenyl-1H-pyrrole-3-carboxamide 1 (50 g) in 280 mL anhydrous THF was added dropwise and maintained at −78° C. for 30 min. After adding 25 mL AcOH and 250 mL water the mixture was allowed to warm to room temperature. The layers were separated and the organic layer was washed and dried. After evaporation of the solvent the crude product was obtained (94 g). Analytical data are consistent with that from the prior art.

Workup

  1. temperaturewas cooled to −78° C
  2. temperaturemaintained at −78° C. for 30 min
  3. temperatureto warm to room temperature
  4. customThe layers were separated
  5. washthe organic layer was washed
  6. customdried
  7. customAfter evaporation of the solvent the crude product
  8. customwas obtained (94 g)

Sources & evidence

ORD record
ord-0ca0fe3ab81a4c498a0e867b0c22545a
Source dataset
uspto-grants-2008_09
Patent number
US07429613B2

Linked notes

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