Quinone → HCID 139986, compound

HRID 1876302Notes

Reaction equation

HRID 1876302 reaction equation
N1(C(O[C@H:10](/[CH:12]=[CH:13]\[C:14]([NH:16][C@@H]2C[C@H](C)[C@H](C/C=C(\C)/C=C)O[C@@H]2C)=[O:15])[CH3:11])=O)CCOCC1.[CH:31]([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])=[CH2:32].C1(=O)C=CC(=O)C=C1>C(Cl)CCl>[CH:31]([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])=[CH2:32].[C:14]([NH2:16])(=[O:15])[CH:13]=[CH:12][CH2:10][CH3:11]

Participants

6

Reactant 3

HCID 4650QuinoneHCID 59552171HCID 59552171, compound2×HCID 59552197HCID 59552197, compound

Product 2

HCID 139986HCID 139986, compoundYield 29%HCID 59552171HCID 59552171, compound

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent2×

Conditions

Temperature
42 °C

Procedure

A solution of (3R,4R,5R)-5-ethenyl-7,7-dimethyl-1,6-dioxaspiro[2.5]octan-4-ol (18 mg, 0.099 mmol) was prepared in ClCH2CH2Cl (200 μL) at 23° C. under an open atmosphere. To a stirred solution of (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 (26 mg, 0.062 mmol) in ClCH2CH2Cl (200 μL) was added the solution of (3R,4R,5R)-5-ethenyl-7,7-dimethyl-1,6-dioxaspiro[2.5]octan-4-ol (100 μL), benzoquinone (1.4 mg, (0.012 mmol), followed by Grela catalyst (1.5 mg, 2.2 μmol) at 23° C. under an open atmosphere. The reaction mixture was then heated to 42° C. After 3 h at the same temperature, additional Grela catalyst (1.5 mg, 2.2 μmol) and (3R,4R,5R)-5-ethenyl-7,7-dimethyl-1,6-dioxaspiro[2.5]octan-4-ol (100 μL) were added. After 11 total hours, 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 (10.4 mg, 29%), and a mixture of (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-ylmorpholine-4-carboxylate and (3R,4R,5R)-5-ethenyl-7,7-dimethyl-1,6-dioxaspiro[2.5]octan-4-ol (22.1 mg).

Workup

  1. concentrationAfter 11 total hours, the 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-3a7199a3f223493fb9c335998a5cac67
Source dataset
uspto-grants-2012_11
Patent number
US08309599B2

Reaction notes

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