Pivalic acid → 1-(2-((4R,6R)-6-(2-(diphenylamino)-2-oxoethyl)-2,2-dimethyl-1,3-dioxan-4-yl)ethyl)-5-(4-fluorophenyl)-2-isopropyl-N,4-diphenyl-1H-pyrrole-3-carboxamide

HRID 2395896Notes

Reaction equation

HRID 2395896 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=O)[CH:9]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH:10]([C:20](=O)[CH:21]([CH3:23])[CH3:22])[C:11]([NH:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[O:12])=[CH:4][CH:3]=1.[NH2:32][CH2:33][CH2:34][C@H:35]1[O:40][C:39]([CH3:42])([CH3:41])[O:38][C@@H:37]([CH2:43][C:44]([N:46]([C:53]2[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=2)[C:47]2[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=2)=[O:45])[CH2:36]1.CCCCCCC.C(O)(=O)C(C)(C)C>C1(C)C=CC=CC=1.O1CCCC1>[C:53]1([N:46]([C:47]2[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=2)[C:44](=[O:45])[CH2:43][C@@H:37]2[O:38][C:39]([CH3:42])([CH3:41])[O:40][C@H:35]([CH2:34][CH2:33][N:32]3[C:8]([C:5]4[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=4)=[C:9]([C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=4)[C:10]([C:11]([NH:13][C:14]4[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=4)=[O:12])=[C:20]3[CH:21]([CH3:23])[CH3:22])[CH2:36]2)[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=1

Participants

7

Reactant 4

HCID 6417Pivalic acidHCID 8900HeptaneHCID 99098724-(4-Fluorophenyl)-2-(2-methyl-1-oxopropyl)-4-oxo-3,N-diphenylbutanamideHCID 109486112-((4R,6R)-6-(2-aminoethyl)-2,2-dimethyl-1,3-dioxan-4-yl)-N,N-diphenylacetamide

Product 1

HCID 111255291-(2-((4R,6R)-6-(2-(diphenylamino)-2-oxoethyl)-2,2-dimethyl-1,3-dioxan-4-yl)ethyl)-5-(4-fluorophenyl)-2-isopropyl-N,4-diphenyl-1H-pyrrole-3-carboxamide

Reagents, catalysts & solvents 2

HCID 1140TolueneSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

A nitrogen purged 500 mL three-neck flask is charged with 4-fluoro-α-(2-methyl-1-oxopropyl)-γ-oxo-N,β-diphenylbenzenebutanamide (Baumann, supra) (13.6 g, 0.032 mol), (4R-cis)-6-(2-aminoethyl)-2,2-dimethyl-N,N-diphenyl-1,3-dioxane-4-acetamide (10.0 g, 0.027 mol), heptane (100 mL) , pivalic acid (3 g), tetrahydrofuran (50 mL), and toluene (60 mL). The mixture is heated to reflux for 48 hours, cooled to room temperature, and diluted with toluene (300 mL). The solution is washed with 0.5N aqueous sodium hydroxide (150 mL), followed by 0.5N aqueous hydrochloric acid (250 mL), and concentrated by vacuum distillation to a foam. The product, (4R-cis)-1-[2-[6-[2-(diphenylamino)-2-oxoethyl]-2,2-dimethyl-1,3-dioxan-4-yl]ethyl]-5-(4-fluorophenyl)-2-(1-methylethyl)-N,4-diphenyl-1H-pyrrole-3-carboxamide, is used in the next step without further purification. Fourier Transform Infrared Spectroscopy (FTIR)(KBr) 3450, 2860, 1650, 1620 cm-1 ;

Workup

  1. customA nitrogen purged 500 mL three-neck flask
  2. temperatureThe mixture is heated
  3. temperatureto reflux for 48 hours
  4. washThe solution is washed with 0.5N aqueous sodium hydroxide (150 mL)
  5. concentrationconcentrated by vacuum distillation to a foam
  6. customThe product, (4R-cis)-1-[2-[6-[2-(diphenylamino)-2-oxoethyl]-2,2-dimethyl-1,3-dioxan-4-yl]ethyl]-5-(4-fluorophenyl)-2-(1-methylethyl)-N,4-diphenyl-1H-pyrrole-3-carboxamide, is used in the next step without further purification

Sources & evidence

ORD record
ord-8062d67640be4f05bbad860a5d83f8e9
Source dataset
uspto-grants-1996_02
Patent number
US05489691

Reaction notes

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