Diisopropylamine → Lithium diisopropylamide

HRID 1604838Notes

Reaction equation

HRID 1604838 reaction equation
[Li:1]CCCC.[CH:6]([NH:9][CH:10]([CH3:12])[CH3:11])([CH3:8])[CH3:7].[CH3:13][O:14][C:15](=[O:25])/[CH:16]=[CH:17]/[CH2:18]P(OC)(OC)=O.[C:26]([Si:30]([CH3:49])([CH3:48])[O:31][C@H:32]1[CH2:41][CH2:40][CH2:39][C@@:38]2([CH3:42])[C@H:33]1[CH2:34][CH2:35][CH:36]=[C:37]2[C@H:43]([CH3:47])[CH2:44][CH:45]=O)([CH3:29])([CH3:28])[CH3:27]>C1COCC1>[Li+:1].[CH3:7][CH:6]([N-:9][CH:10]([CH3:12])[CH3:11])[CH3:8].[CH3:13][O:14][C:15](=[O:25])/[CH:16]=[CH:17]/[CH:18]=[CH:45]/[CH2:44][C@H:43]([C:37]1[C@:38]2([CH3:42])[C@H:33]([C@@H:32]([O:31][Si:30]([C:26]([CH3:28])([CH3:27])[CH3:29])([CH3:48])[CH3:49])[CH2:41][CH2:40][CH2:39]2)[CH2:34][CH2:35][CH:36]=1)[CH3:47]

Participants

7

Reactant 4

HCID 7912DiisopropylamineHCID 5702556Trimethyl 4-phosphonocrotonateHCID 57177837(R)-3-[(4aR,5S,8aS)-5-(tert-butyldimethyl-silanyloxy)-8a-methyl-3,4,4a,5,6,7,8,8a-octahydro-naphthalen-1-yl]-butyraldehydeHCID 178418339Butyllithium

Product 2

HCID 2724682Lithium diisopropylamideHCID 86754889(2E,4E)-(R)-7-[(4aR,5S,8aS)-5-(tert-butyldimethyl-silanyloxy)-8a-methyl-3,4,4a,5,6,7,8,8a-octahydro-naphthalen-1-yl]-octa-2,4-dienoic acid methyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A LDA solution was prepared by adding at 0° 9.79 ml of nBuLi (1.55 M, hexane) to 2.30 ml of diisopropylamine. After cooling to -78°, 2.872 g of (E)-4-(dimethoxy-phosphoryl)-but-2-enoic acid methyl ester, dissolved in 17 ml of abs. THF, were added. 90 minutes later, 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 dissolved in 15 ml of abs. THF, were added and allowed to react for 2 h at -78° and 1.5 h at -40°. The mixture was then poured onto crushed ice/NH4Cl, extracted with ether, washed with brine, dried over magnesium sulfate, and evaporated to dryness. Flash chromatography (SiO2, hexane/AcOEt=97/3), followed by MPLC (SiO2, hexane/AcOEt=98.9/1.9) and crystallization from hexane, yielded 1.367 g of (2E,4E)-(R)-7-[(4aR,5S,8aS)-5-(tert-butyldimethyl-silanyloxy)-8a-methyl-3,4,4a,5,6,7,8,8a-octahydro-naphthalen-1-yl]-octa-2,4-dienoic acid methyl ester as white crystals of mp. 59-64°.

Workup

  1. temperatureAfter cooling to -78°
  2. customto react for 2 h at -78° and 1.5 h at -40°
  3. additionThe mixture was then poured
  4. extractionextracted with ether
  5. washwashed with brine
  6. dry with materialdried over magnesium sulfate
  7. customevaporated to dryness
  8. customFlash chromatography (SiO2, hexane/AcOEt=97/3), followed by MPLC (SiO2, hexane/AcOEt=98.9/1.9) and crystallization from hexane

Sources & evidence

ORD record
ord-09ad2d691e4a4813b36f63af58635271
Source dataset
uspto-grants-1999_11
Patent number
US05994569

Reaction notes

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