Triphenylphosphine → HCID 67299228, compound

HRID 2193944Notes

Reaction equation

HRID 2193944 reaction equation
[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[CH:8][C:9]=1[NH:10][CH:11]([CH3:13])[CH3:12])=[O:4].[C:20]([O:23][C@H:24]1[CH2:29][C@H:28]([CH3:30])[CH2:27][CH2:26][C@H:25]1[C:31](Cl)=[O:32])(=[O:22])[CH3:21].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C([O-])(O)=O.[Na+]>ClCCCl.C(OCC)(=O)C>[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)=[CH:8][C:9]=1[N:10]([CH:11]([CH3:13])[CH3:12])[C:31]([C@@H:25]1[CH2:26][CH2:27][C@@H:28]([CH3:30])[CH2:29][C@@H:24]1[O:23][C:20](=[O:22])[CH3:21])=[O:32])=[O:4]

Participants

7

Reactant 4

HCID 11776TriphenylphosphineHCID 516892Sodium BicarbonateHCID 11737447Methyl 3-(isopropyl-amino)-5-phenylthiophene-2-carboxylateHCID 59752362HCID 59752362, compound

Product 1

HCID 67299228HCID 67299228, compoundYield 48.1%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of 3-Isopropylamino-5-phenyl-thiophene-2-carboxylic acid methyl ester (136 mg, 0.50 mmol) in 1,2-dichloroethane (1.0 ml) was added (1R,2S,4R)-2-Acetoxy-4-methyl-cyclohexanecarboxylic acid chloride (119 mg, 0.54 mmol) dissolved in 1,2-dichloroethane (0.6 ml) followed by PPh3 (136 mg, 0.52 mmol). The resulting solution was stirred for 20 h at 90° C. and then cooled to room temperature. It was then diluted with ethyl acetate (10 ml) and a solution of saturated NaHCO3 (10 ml). The aqueous phase was separated and washed with ethyl acetate (2×10 ml) and the combined organic layers were dried (Na2SO4), filtered and concentrated. The residue was purified by flash chromatography (0% to 25% EtOAc/Hexane) to obtain 110 mg (45%) of (1R,2S,4R)-3-[Isopropyl-(2-Acetoxy-4-methyl-cyclohexanecarbonyl)-amino]-5-phenyl-thiophene-2-carboxylic acid methyl ester. NMR 1H (CDCl3, 400 MHz): 1.5:1.0 mixture of rotamers 7.73-7.70 ppm (m, 2H, Haro); 7.69-7.63 ppm (m, 1H, Haro); 7.51-7.41 ppm (m, 4H, Haro); 7.13 ppm (s, 0.6H, Haro, major rotamer); 5.79 ppm (s, 0.4H, minor rotamer); 5.21 ppm (s, 0.6H, major rotamer); 4.95-4.88 ppm (m, 1H); 3.88 ppm (s, 1.8H, major rotamer); 3.87 ppm (s, 1.2H, minor rotamer); 2.40-2.36 ppm (m, 0.6H, major rotamer); 2.11 ppm (s, 3H); 1.78-0.77 ppm (m, 16H).

Workup

  1. temperaturecooled to room temperature
  2. customThe aqueous phase was separated
  3. washwashed with ethyl acetate (2×10 ml)
  4. dry with materialthe combined organic layers were dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by flash chromatography (0% to 25% EtOAc/Hexane)

Sources & evidence

ORD record
ord-a6124cae05d54899a4ba7d53217686a2
Source dataset
uspto-grants-2012_12
Patent number
US08329924B2

Reaction notes

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