5-(3-((R)-3,3-difluoro-5-((3S,4S,E)-3-hydroxy-4-methyl-7-phenylhept-1-en-1-yl)-2-oxopyrrolidin-1-yl)propyl)thiophene-2-carboxylic acid → HCID 90054450, compound

HRID 709117Notes

Reaction equation

HRID 709117 reaction equation
[F:1][C:2]1([F:34])[CH2:6][C@H:5](/[CH:7]=[CH:8]/[C@@H:9]([OH:21])[C@@H:10]([CH3:20])[CH2:11][CH2:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[N:4]([CH2:22][CH2:23][CH2:24][C:25]2[S:29][C:28]([C:30]([OH:32])=[O:31])=[CH:27][CH:26]=2)[C:3]1=[O:33].[H][H]>C(O)C.[Pd]>[F:34][C:2]1([F:1])[CH2:6][C@H:5]([CH2:7][CH2:8][C@@H:9]([OH:21])[C@@H:10]([CH3:20])[CH2:11][CH2:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[N:4]([CH2:22][CH2:23][CH2:24][C:25]2[S:29][C:28]([C:30]([OH:32])=[O:31])=[CH:27][CH:26]=2)[C:3]1=[O:33]

Participants

5

Reactant 2

HCID 729484795-(3-((R)-3,3-difluoro-5-((3S,4S,E)-3-hydroxy-4-methyl-7-phenylhept-1-en-1-yl)-2-oxopyrrolidin-1-yl)propyl)thiophene-2-carboxylic acidHCID 178418361HCID 178418361, compound2×

Product 1

HCID 90054450HCID 90054450, compoundYield 62.1%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

To a solution consisting of 5-(3-((R)-3,3-difluoro-5-((3S,4S,E)-3-hydroxy-4-methyl-7-phenylhept-1-en-1-yl)-2-oxopyrrolidin-1-yl)propyl)thiophene-2-carboxylic acid (15.2 mg, 0.031 mmol) in ethanol (12 mL) and covered with an atmosphere of nitrogen was added palladium (12 mg, 10% on activated carbon). The nitrogen atmosphere was replaced with hydrogen and the reaction mixture was stirred vigorously for 5 hours at room temperature. The hydrogen was replaced with nitrogen and mixture was filtered through a small pad of celite which was washed with ethanol. The combined filtrate was concentrated under vacuum and the residue was purified by silica gel chromatography eluting with ethyl acetate-heptane-acetic acid (45:55:0.4 v/v/v) to give 9.5 mg (62%) of the title compound as a colorless oil; TLC Rf 0.29 (solvent system: 45:55:1 v/v/v ethyl acetate-heptane-acetic acid); MS (ESI−) m/z 492.2 (M−H)−; 1H NMR (CD3OD) δ 7.47 (d, J=3.66 Hz, 1H), 7.18-7.01 (m, 5H), 6.80 (d, J=3.30 Hz, 1H), 3.72-3.63 (m, 1H), 3.16-3.03 (m, 1H), 2.79 (t, J=7.32 Hz, 2H), 2.61-2.45 (m, 3H), 2.19-2.05 (m, 1H), 1.98-1.78 (m, 2H), 1.78-1.57 (m, 2H), 1.53-1.39 (m, 4H), 1.34-1.14 (m, 5H), 1.10-1.00 (m, 1H), 0.81-0.76 (m, 3H); 19F NMR (CD3OD) δ−103.2 (ddd, 1F), −105.9 (ddd, 1F).

Workup

  1. filtrationwas filtered through a small pad of celite which
  2. washwas washed with ethanol
  3. concentrationThe combined filtrate was concentrated under vacuum
  4. customthe residue was purified by silica gel chromatography
  5. washeluting with ethyl acetate-heptane-acetic acid (45:55:0.4 v/v/v)

Sources & evidence

ORD record
ord-2cd997af7ad04a5fa9a9b661ce11f9c6
Source dataset
uspto-grants-2015_11
Patent number
US09180116B2

Reaction notes

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