Formaldehyde → (S)-2-[(4aR,5S,8aS)-5-(tert-butyldimethyl-silanyloxy)-8a-methyl-3,4,4a,5,6,7,8,8a-octahydronaphthalen-1-yl]-propan-1-ol

HRID 1859003Notes

Reaction equation

HRID 1859003 reaction equation
[C:1]([Si:5]([O:8][C@@H:9]1[C@H:18]2[C@@:13]([CH3:21])([C:14](=CC)[CH2:15][CH2:16][CH2:17]2)[CH2:12][CH2:11][CH2:10]1)([CH3:7])[CH3:6])([CH3:4])([CH3:3])[CH3:2].[CH2:22]=O.[Cl-].C[Al+]C.C([O:30][CH2:31][CH3:32])C>C1(C)C=CC=CC=1.CCCCCC>[C:1]([Si:5]([CH3:7])([CH3:6])[O:8][C@H:9]1[CH2:10][CH2:11][CH2:12][C@@:13]2([CH3:21])[C@H:18]1[CH2:17][CH2:16][CH:15]=[C:14]2[C@H:32]([CH3:22])[CH2:31][OH:30])([CH3:3])([CH3:4])[CH3:2]

Participants

7

Reactant 4

HCID 712FormaldehydeHCID 3283Diethyl EtherHCID 16686359Dimethylalumanylium chlorideHCID 57178905(1S,4aS,8aR)-tert-Butyl-(5-ethylidene-4a-methyl-decahydro-naphtalen-1-yloxy)-dimethyl-silane

Product 1

HCID 21309369(S)-2-[(4aR,5S,8aS)-5-(tert-butyldimethyl-silanyloxy)-8a-methyl-3,4,4a,5,6,7,8,8a-octahydronaphthalen-1-yl]-propan-1-olYield 67.5%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8058HexaneSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of 3.11 g (10.1 mMol) of (1S,4aS,8aR)-tert-Butyl-(5-ethylidene-4a-methyl-decahydro-naphtalen-1-yloxy)-dimethylsilane in 125 ml of toluene are added 0.33 g (11.1 mMol) of finely powdered paraformaldehyde. The reaction mixture is cooled to 0° C. and 12.56 ml of a one molar solution of dimethylaluminumchloride in hexane are added and kept for one hour at this temperature. The reaction mixture is stirred at room temperature overnight, diluted with diethylether, washed with 1N HCl and with water, then dried over sodium sulfate and evaporated in vacuo. The residue is chromatographed over a medium pressure 250 g silicagel column with hexane/ethylacetate 9/1 to yield 2.31 g (67.5%) of pure (S)-2-[(4aR,5S,8aS)-5-(tert-butyl-dimethyl-silanyloxy)-8a-methyl-3,4,4a,5,6,7,8,8a-octahydro-naphtalen-1-yl]-propan-1-ol as an oil. By running the reaction with BF3.Et2O in CH2Cl2 small amounts of the (R)-epimer, the starting material of Examples 31-33 can be isolated.

Workup

  1. washwashed with 1N HCl and with water
  2. dry with materialdried over sodium sulfate
  3. customevaporated in vacuo
  4. customThe residue is chromatographed over a medium pressure 250 g silicagel column with hexane/ethylacetate 9/1

Sources & evidence

ORD record
ord-f6c9373108f94647ad4816c66240799c
Source dataset
uspto-grants-2000_11
Patent number
US06153605

Reaction notes

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