Toluene → (1S,2R,4aS,8aS)-1-(3-methoxy-5-methylphenoxymethyl)-2,5,5,8a-tetramethyl-decahydronaphthalen-2-ol

HRID 422126

Reaction equation

HRID 422126 reaction equation
[OH:1][CH2:2][C@@H:3]1[C@:12]2([CH3:13])[C@H:7]([C:8]([CH3:15])([CH3:14])[CH2:9][CH2:10][CH2:11]2)[CH2:6][CH2:5][C@@:4]1([CH3:17])[OH:16].CC1C=NC2C(C=1C)=CC=C1C=2N=CC(C)=C1C.C1(C)C=CC=CC=1.I[C:44]1[CH:49]=[C:48]([CH3:50])[CH:47]=[C:46]([O:51][CH3:52])[CH:45]=1>COCCOCCOC>[CH3:52][O:51][C:46]1[CH:45]=[C:44]([CH:49]=[C:48]([CH3:50])[CH:47]=1)[O:1][CH2:2][C@@H:3]1[C@:12]2([CH3:13])[C@H:7]([C:8]([CH3:15])([CH3:14])[CH2:9][CH2:10][CH2:11]2)[CH2:6][CH2:5][C@@:4]1([CH3:17])[OH:16]

Participants

6

Reactant 4

HCID 1140TolueneHCID 742653,4,7,8-Tetramethyl-1,10-phenanthrolineHCID 10879261(1S,2R,4aS,8aS)-1-(hydroxymethyl)-2,5,5,8a-tetramethyl-decahydronaphthalen-2-olHCID 187197941-Iodo-3-methoxy-5-methylbenzene

Product 1

HCID 66673282(1S,2R,4aS,8aS)-1-(3-methoxy-5-methylphenoxymethyl)-2,5,5,8a-tetramethyl-decahydronaphthalen-2-olYield 92%

Reagents, catalysts & solvents 1

HCID 8150DiglymeSolvent

Procedure

(1S,2R,4aS,8aS)-1-(hydroxymethyl)-2,5,5,8a-tetramethyl-decahydronaphthalen-2-ol (3) (prepared according to Kuchkova et al., Synthesis, 1045-1048, 1997) (0.24 g, 1.0 mmol), Cu(I)I (0.019 g, 0.10 mmol)) and 3,4,7,8-tetramethyl-[1,10]phenanthroline (0.047 g, 0.20 mmol)) were added to an oven dried sealed tube, sealed with a rubber septum, and flushed with a stream of nitrogen for 15 min. Anhydrous toluene (5 mL), anhydrous diglyme (1 mL) and 1-iodo-3-methoxy-5-methylbenzene (2) (0.273 g, 1.10 mmol) were added via a syringe with vigorous stirring under a stream of nitrogen at room temperature. The rubber septum was replaced with the Teflon cap and the sealed tube was heated at 120° C. in an oil bath for 18 h. The reaction was allowed to cool to room temperature, and then quenched with ethyl acetate. The resulting suspension was filtered through a celite pad. The filtrate and the washings were concentrated to dryness. The crude product was purified by flash chromatography (Hexanes/EtOAc, 9:1) to yield (1S,2R,4aS,8aS)-1-(3-methoxy-5-methylphenoxymethyl)-2,5,5,8a-tetramethyl-decahydronaphthalen-2-ol (4) (0.33 g, 92% yield) as a pale yellow solid.

Workup

  1. customdried
  2. customsealed tube
  3. customsealed with a rubber septum
  4. customflushed with a stream of nitrogen for 15 min
  5. customcap
  6. temperaturethe sealed tube was heated at 120° C. in an oil bath for 18 h
  7. temperatureto cool to room temperature
  8. customquenched with ethyl acetate
  9. filtrationThe resulting suspension was filtered through a celite pad
  10. concentrationThe filtrate and the washings were concentrated to dryness
  11. customThe crude product was purified by flash chromatography (Hexanes/EtOAc, 9:1)

Sources & evidence

ORD record
ord-ebd569e9373d488fb748d733b6f74b86
Source dataset
uspto-grants-2012_01
Patent number
US08101605B2

Linked notes

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