Methoxymethyl-triphenylphosphonium chloride → (R)-3-[(4aR,5S,8aS)-5-(tert-butyldimethyl-silanyloxy)-8a-methyl-3,4,4a,5,6,7,8,8a-octahydro-naphthalen-1-yl]-butyraldehyde

HRID 1604837Notes

Reaction equation

HRID 1604837 reaction equation
[Cl-].C[O:3]C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Li]CC[CH2:27][CH3:28].[C:29]([Si:33]([CH3:51])([CH3:50])[O:34][C@H:35]1[CH2:44][CH2:43][CH2:42][C@@:41]2([CH3:45])[C@H:36]1[CH2:37][CH2:38][CH:39]=[C:40]2[C@H:46]([CH3:49])C=O)([CH3:32])([CH3:31])[CH3:30]>C1COCC1>[C:29]([Si:33]([CH3:51])([CH3:50])[O:34][C@H:35]1[CH2:44][CH2:43][CH2:42][C@@:41]2([CH3:45])[C@H:36]1[CH2:37][CH2:38][CH:39]=[C:40]2[C@H:46]([CH3:49])[CH2:28][CH:27]=[O:3])([CH3:31])([CH3:32])[CH3:30]

Participants

5

Reactant 3

HCID 2723798Methoxymethyl-triphenylphosphonium chlorideHCID 21310065(S)-2-[(4aR,5S,8aS)-5-(tert-butyldimethyl-silanyloxy)-8a-methyl-3,4,4a,5,6,7,8,8a-octa-hydro-naphthalen-1-yl]-propionaldehydeHCID 178418339Butyllithium

Product 1

HCID 57177837(R)-3-[(4aR,5S,8aS)-5-(tert-butyldimethyl-silanyloxy)-8a-methyl-3,4,4a,5,6,7,8,8a-octahydro-naphthalen-1-yl]-butyraldehyde

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A suspension of 7.17 g of (methoxymethyl)triphenylphosphonium chloride in 50 ml of abs. THF was cooled to -20° and treated with 12.1 ml of nBuLi (1.55 M, hexane). 30 minutes later, the deep red ylide solution was cooled down to -78° and 3.525 g of (S)-2-[(4aR,5S,8aS)-5-(tert-butyldimethyl-silanyloxy)-8a-methyl-3,4,4a,5,6,7,8,8a-octa-hydronaphthalen-1-yl]-propionaldehyde dissolved in 21 ml of abs. THF, were slowly added and the reaction mixture kept for 45 minutes at that temperature. Partition between hexane and EtOH/H2O=8/2, washing of the upper layer with EtOH/H2O=8/2, drying over magnesium sulfate, evaporating i. V. and flash chromatography (SiO2, hexane/AcOEt=99/1) generated 2.590 g of an enolether intermediate as E/Z-mixture. This enolether was hydrolyzed by dissolving it in 30 ml of THF containing 10 ml of 25% aq. HCl. After 90 minutes at ambient temperature, the reaction mixture was poured onto crushed ice, extracted with ether, washed with water and brine, dried over magnesium sulfate and evaporated to dryness. Flash chromatography (SiO2, hexane/AcOEt=98/2) yielded 2.424 g of (R)-3-[(4aR,5S,8aS)-5-(tert-butyldimethyl-silanyloxy)-8a-methyl-3,4,4a,5,6,7,8,8a-octahydro-naphthalen-1-yl]-butyraldehyde as yellowish oil.

Workup

  1. temperature30 minutes later, the deep red ylide solution was cooled down to -78°
  2. customPartition between hexane and EtOH/H2O=8/2
  3. washwashing of the upper layer with EtOH/H2O=8/2
  4. dry with materialdrying over magnesium sulfate
  5. customevaporating i
  6. dissolutionby dissolving it in 30 ml of THF containing 10 ml of 25% aq. HCl
  7. waitAfter 90 minutes at ambient temperature
  8. additionthe reaction mixture was poured
  9. customonto crushed ice
  10. extractionextracted with ether
  11. washwashed with water and brine
  12. dry with materialdried over magnesium sulfate
  13. customevaporated to dryness

Sources & evidence

ORD record
ord-a69a03d6312e4764ba6d14193916a2e9
Source dataset
uspto-grants-1999_11
Patent number
US05994569

Reaction notes

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