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

HRID 1604832Notes

Reaction equation

HRID 1604832 reaction equation
[Cl-].C[O:3]C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Li][CH2:25][CH2:26][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][CH2:39][C@@H:40]2[C@H](C)C=O)([CH3:32])([CH3:31])[CH3:30]>C1COCC1>[C:29]([Si:33]([CH3:50])([CH3:51])[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][CH2:39][C@@H:40]2[C@H:27]([CH3:28])[CH2:26][CH:25]=[O:3])([CH3:31])([CH3:30])[CH3:32]

Participants

5

Reactant 3

HCID 2723798Methoxymethyl-triphenylphosphonium chlorideHCID 57255936(S)-2-[(1R,4aR,5S,8aR)-5-(tert-butyldimethyl-silanyloxy)-8a-methyl-decahydro-naphthalen-1-yl]-propionaldehydeHCID 178418339Butyllithium

Product 1

HCID 57316286(R)-3-[(1R,4aR,5S,8aR)-5-(tert-butyldimethyl-silanyloxy)-8a-methyl-decahydro-naphthalen-1-yl]-butyraldehyde

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A suspension of 6.54 g of (methoxymethyl)triphenylphosphonium chloride in 38 ml of abs. THF was cooled to -10° and treated with 11.3 ml of nBuLi (1.5 M, hexane). 15 minutes later, the deep red ylide solution was cooled down to -78° and 3.225 g of (S)-2-[(1R,4aR,5S,8aR)-5-(tert-butyldimethyl-silanyloxy)-8a-methyl-decahydro-naphthalen-1-yl]-propionaldehyde dissolved in 21 ml of abs. THF, were slowly added and the reaction mixture kept for 60 minutes at that temperature. Partition between hexane and EtOH/H2O=8/2, washing of the upper layer with EtOH/H2O=8/2, drying over sodium sulfate, evaporating i. V. and flash chromatography (SiO2, hexane/AcOEt=98/2) delivered 3.11 g of an enolether intermediate as E/Z-mixture, contaminated with some impurities which were removed after the next step. This enolether was hydrolyzed by dissolving it in 35 ml of THF containing 12.5 ml of 25% aq. HCl. After 2.5 h at ambient temperature, the reaction mixture was poured onto crushed ice, extracted with ether, washed with water and brine, dried over sodium sulfate and evaporated to dryness. Flash chromatography (SiO2, hexane/AcOEt=98/2) yielded 1.76 g of (R)-3-[(1R,4aR,5S,8aR)-5-(tert-butyldimethyl-silanyloxy)-8a-methyl-decahydro-naphthalen-1-yl]-butyraldehyde as colourless oil.

Workup

  1. temperature15 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 sodium sulfate
  5. customevaporating i
  6. customwere removed after the next step
  7. dissolutionby dissolving it in 35 ml of THF containing 12.5 ml of 25% aq. HCl
  8. waitAfter 2.5 h at ambient temperature
  9. additionthe reaction mixture was poured
  10. customonto crushed ice
  11. extractionextracted with ether
  12. washwashed with water and brine
  13. dry with materialdried over sodium sulfate
  14. customevaporated to dryness

Sources & evidence

ORD record
ord-066e7d8f87cd4a6ea871bf421ad13729
Source dataset
uspto-grants-1999_11
Patent number
US05994569

Reaction notes

Loading…