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 1757460Notes

Reaction equation

HRID 1757460 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 concentratedby 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. distillationfollowed by 0.5N aqueous hydrochloric acid (250 mL), and concentratedby 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-df8e54854e84436fa1cac88b6b1d5a02
Source dataset
uspto-grants-1995_08
Patent number
US05446054

Reaction notes

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