Quinone → HCID 25025434, compound

HRID 1170406Notes

Reaction equation

HRID 1170406 reaction equation
[N:1]1([C:7]([O:9][C@H:10](/[CH:12]=[CH:13]\[C:14]([NH:16][C@@H:17]2[CH2:22][C@H:21]([CH3:23])[C@H:20]([CH2:24]/[CH:25]=[C:26](\[CH3:29])/[CH:27]=[CH2:28])[O:19][C@@H:18]2[CH3:30])=[O:15])[CH3:11])=[O:8])[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.C([C@H:33]1[O:40][C:39]([CH3:42])([CH3:41])[CH2:38][C@:35]2([O:37][CH2:36]2)[C@@H:34]1[OH:43])=C.C1(=O)C=CC(=O)C=C1>C(Cl)CCl>[N:1]1([C:7]([O:9][C@@H:10]([CH3:11])/[CH:12]=[CH:13]\[C:14]([NH:16][C@@H:17]2[CH2:22][C@H:21]([CH3:23])[C@H:20]([CH2:24]/[CH:25]=[C:26](\[CH3:29])/[CH:27]=[CH:28]/[C@H:33]3[O:40][C:39]([CH3:41])([CH3:42])[CH2:38][C@:35]4([O:37][CH2:36]4)[C@@H:34]3[OH:43])[O:19][C@@H:18]2[CH3:30])=[O:15])=[O:8])[CH2:2][CH2:3][O:4][CH2:5][CH2:6]1

Participants

5

Reactant 3

HCID 4650QuinoneHCID 59552171HCID 59552171, compoundHCID 59552197HCID 59552197, compound

Product 1

HCID 25025434HCID 25025434, compound

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Conditions

Temperature
42 °C

Procedure

To a stirred solution of recovered (S,Z)-5-((2R,3R,5S,6S)-2,5-dimethyl-6-((E)-3-methylpenta-2,4-dienyl)-tetrahydro-2H-pyran-3-ylamino)-5-oxopent-3-en-2-yl morpholine-4-carboxylate and (3R,4R,5R)-5-ethenyl-7,7-dimethyl-1,6-dioxaspiro[2.5]octan-4-ol (22.1 mg) in ClCH2CH2Cl (200 μL) was added benzoquinone (1.0 mg, 0.010 mmol) and Grela Catalyst (2.0 mg, 3.0 μmol) at 23° C. under an open atmosphere. The reaction mixture was then heated to 42° C. After an additional 14 h at the same temperature, the reaction was concentrated under reduced pressure. The resulting residue was purified by flash chromatography (10→80% EtOAc in hexanes) on silica gel (8 mL) to give (2Z,4S)-4-[(morpholinylcarbonyl)oxy]-N-[(2R,3R,5S,6S)-tetrahydro-6-[(2E,4E)-5-[(3R,4R,5R)-4-hydroxy-7,7-dimethyl-1,6-dioxaspiro[2.5]oct-5-yl]-3-methyl-2,4-pentadien-1-yl]-2,5-dimethyl-2H-pyran-3-yl]-2-pentenamide as a pale tan solid. The combined yield of (2Z,4S)-4-[(morpholinylcarbonyl)oxy]-N-[(2R,3R,5S,6S)-tetrahydro-6-[(2E,4E)-5-[(3R,4R,5R)-4-hydroxy-7,7-dimethyl-1,6-dioxaspiro[2.5]oct-5-yl]-3-methyl-2,4-pentadien-1-yl]-2,5-dimethyl-2H-pyran-3-yl]-2-pentenamide after one cycle is 15.7 mg (44%). Some of the tan (2Z,4S)-4-[(morpholinylcarbonyl)oxy]-N-[(2R,3R,5S,6S)-tetrahydro-6-[(2E,4E)-5-[(3R,4R,5R)-4-hydroxy-7,7-dimethyl-1,6-dioxaspiro[2.5]oct-5-yl]-3-methyl-2,4-pentadien-1-yl]-2,5-dimethyl-2H-pyran-3-yl]-2-pentenamide was purified by semi-preparative HPLC (Conditions: flow rate=2.5 mL, from 30% to 100% MeCN in H2O over 30 min; Column=Varian Pursuit XRs C18 column (5 μm packing, 250×10 mm); Retention time 16.70 min; Detection=237 nm) to afford (2Z,4S)-4-[(morpholinylcarbonyl)oxy]-N-[(2R,3R,5S,6S)-tetrahydro-6-[(2E,4E)-5-[(3R,4R,5R)-4-hydroxy-7,7-dimethyl-1,6-dioxaspiro[2.5]oct-5-yl]-3-methyl-2,4-pentadien-1-yl]-2,5-dimethyl-2H-pyran-3-yl]-2-pentenamide as a colorless oil that was subsequently used for biological experiments.

Workup

  1. concentrationthe reaction was concentrated under reduced pressure
  2. customThe resulting residue was purified by flash chromatography (10→80% EtOAc in hexanes) on silica gel (8 mL)

Sources & evidence

ORD record
ord-afe232465bb248ea999aca7b8decbc93
Source dataset
uspto-grants-2010_11
Patent number
US07825267B2

Reaction notes

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