Acetic Acid → 6-[(E)-3-tert-butyldimethylsilyloxy-3-cyclohexylprop-1-enyl]-3-(5-ethoxycarbonyl-2-hydroxypent-2-yl)bicyclo[3,3,0]octan-2-one

HRID 462798Notes

Reaction equation

HRID 462798 reaction equation
[Si:1]([O:8][CH:9]([CH:21]1[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]1)/[CH:10]=[CH:11]/[CH:12]1[CH2:19][CH2:18][CH:17]2[CH:13]1[CH2:14][CH2:15][C:16]2=[O:20])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[O:37]=[C:38]([CH3:47])[CH2:39][CH2:40][CH2:41][C:42]([O:44][CH2:45][CH3:46])=[O:43].C(O)(=O)C>O1CCCC1.C(OCC)C.O>[Si:1]([O:8][CH:9]([CH:21]1[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]1)/[CH:10]=[CH:11]/[CH:12]1[CH2:19][CH2:18][CH:17]2[CH:13]1[CH2:14][CH:15]([C:38]([OH:37])([CH2:39][CH2:40][CH2:41][C:42]([O:44][CH2:45][CH3:46])=[O:43])[CH3:47])[C:16]2=[O:20])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]

Participants

8

Reactant 4

HCID 176Acetic AcidHCID 84130Ethyl 5-oxohexanoateHCID 2733832Lithium HexamethyldisilazideHCID 13241020(E)-2-(3-tert-Butyldimethylsilyloxy-3-cyclohexylprop-1-enyl)bicyclo[3,3,0]octan-6-one

Product 1

HCID 203972076-[(E)-3-tert-butyldimethylsilyloxy-3-cyclohexylprop-1-enyl]-3-(5-ethoxycarbonyl-2-hydroxypent-2-yl)bicyclo[3,3,0]octan-2-oneYield 23.8%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-70 °C

Procedure

(E)-2-(3-tert-Butyldimethylsilyloxy-3-cyclohexylprop-1-enyl)bicyclo[3,3,0]octan-6-one, (65 mg), prepared as described in Reference Example 37 and in the form of (±)-(E)-2β-(3β-tert-butyldimethylsilyloxy-3-cyclohexylprop-1-enyl)bicyclo[3,3,0]octan-6-one was dissolved in dry tetrahydrofuran (2.63 ml). The solution was cooled to to -70° C. under an atmosphere of argon and treated with a solution of lithium bis(trimethylsilyl)amide in tetrahydrofuran (0.212 ml; 1M), and the mixture was stirred at -70° C. for 10 minutes. The mixture was then treated with ethyl 5-oxohexanoate (55 mg) and stirred for a further period of 5 hours at -70° C. The solution was treated with a solution of glacial acetic acid (0.02 ml) in diethyl ether (0.175 ml) and the mixture was allowed to warm to the ambient temperature. The mixture was then treated with water (20 ml) and extracted with ethyl acetate. The extract was washed with saturated aqueous sodium bicarbonate solution and then with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulphate, and concentrated under reduced pressure. The residual oil was subjected to medium pressure, short column chromatography on silica gel, using a mixture of ethyl acetate and hexane (1:6 v/v) as eluant, to give 6-[(E)-3-tert-butyldimethylsilyloxy-3-cyclohexylprop-1-enyl]-3-(5-ethoxycarbonyl-2-hydroxypent-2-yl)bicyclo[3,3,0]octan-2 -one (22 mg), in the form of 6β-[(E)-3β-tert-butyldimethylsilyloxy-3-cyclohexylprop-1-enyl]-3-(5-ethoxycarbonyl-2-hydroxypent-2-yl)bicyclo[3,3,0]octan-2-one, otherwise known as (±)-ethyl(13E)-(9S,15R)-6a-oxo-6,9-methano-15-tert-butyldimethylsilyloxy-15-cyclohexyl-5-hydroxy-5-methyl-16,17,18,19,20-pentanorprosta-13-dienoate.

Workup

  1. stirringstirred for a further period of 5 hours at -70° C
  2. temperatureto warm to the ambient temperature
  3. extractionextracted with ethyl acetate
  4. washThe extract was washed with saturated aqueous sodium bicarbonate solution
  5. dry with materialwith saturated aqueous sodium chloride solution, dried over anhydrous sodium sulphate
  6. concentrationconcentrated under reduced pressure
  7. additiona mixture of ethyl acetate and hexane (1:6 v/v) as eluant

Sources & evidence

ORD record
ord-94145d1f0e4d4008a027c6efeac5a37d
Source dataset
uspto-grants-1985_05
Patent number
US04517202

Reaction notes

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