tert-Butyl acetate → t-Butyl (S)-5-hydroxy-3-oxo-6-(triphenylmethoxy)hexanoate

HRID 1608383Notes

Reaction equation

HRID 1608383 reaction equation
[C:1]([O:4][C:5]([CH3:8])([CH3:7])[CH3:6])(=[O:3])[CH3:2].[OH:9][C@H:10]([CH2:16][O:17][C:18]([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[CH2:11][C:12](OC)=[O:13].[Li]CC(OC(C)(C)C)=O.[Cl-].[NH4+]>C(OCC)(=O)C.O1CCCC1>[OH:9][C@H:10]([CH2:16][O:17][C:18]([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)([C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[CH2:11][C:12](=[O:13])[CH2:2][C:1]([O:4][C:5]([CH3:8])([CH3:7])[CH3:6])=[O:3]

Participants

7

Reactant 4

HCID 10908tert-Butyl acetateHCID 25517Ammonium ChlorideHCID 14391030(S)-Methyl 3-hydroxy-4-(trityloxy)butanoateHCID 178506879HCID 178506879, compound

Product 1

HCID 15702750t-Butyl (S)-5-hydroxy-3-oxo-6-(triphenylmethoxy)hexanoateYield 126.2%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-70 °C

Procedure

Under a nitrogen atmosphere and at 0° C., 87.78 ml. of 1.5M. n-butyllithium/hexane (132 mmoles) is added dropwise to 18.49 ml. (132 mmoles) of diisopropylamine in 150 ml. of dry tetrahydrofuran, and the mixture is stirred for 30 minutes to form a solution of lithium diisopropylamide. The obtained solution is cooled to -70° C., a solution of 17.76 ml. (132 mmoles) of t-butyl acetate in 25 ml. of dry tetrahydrofuran is added over a period of 1 hour with stirring at -65°--70° C., the reaction mixture is stirred for 1.5 hours at the same temperature, a solution of 11.28 g. (30 mmoles) of methyl (S)-3-hydroxy-4-(triphenylmethoxy)butanoate (obtainable by Step 3 of Example 1) in 75 ml. of dry tetrahydrofuran is added to the obtained solution of t-butyl lithioacetate at -65°--70° C., and the yellow solution is stirred at about - 70° C. for 0.5 hour, warmed to -10° C. and stirred at -10° C. for 1 hour (with thin layer chromatography (TLC) monitoring to indicate when the reaction is over), the reaction mixture being stirred under nitrogen throughout. 150 ml. of saturated aqueous ammonium chloride is added to quench the reaction at -60°--70° C., the mixture is warmed to 0° C., transferred to a separatory funnel and diluted with ethyl acetate, and the organic phase is separated. The aqueous layer is extracted with an additional 200 ml. of ethyl acetate, and the organic phases are combined, washed successively with 90 ml. of 1N. hydrochloric acid and 90 ml. of saturated aqueous sodium bicarbonate, dried and filtered. The organic solution is evaporated to yield the crude product (17.43 g.) (estimated to be about 80% pure by chromatography analysis).

Workup

  1. stirringthe reaction mixture is stirred for 1.5 hours at the same temperature
  2. stirringthe yellow solution is stirred at about - 70° C. for 0.5 hour
  3. temperaturewarmed to -10° C.
  4. stirringstirred at -10° C. for 1 hour (with thin layer chromatography (TLC) monitoring
  5. stirringbeing stirred under nitrogen throughout
  6. customto quench
  7. customthe reaction at -60°--70° C.
  8. temperaturethe mixture is warmed to 0° C.
  9. customtransferred to a separatory funnel
  10. customthe organic phase is separated
  11. extractionThe aqueous layer is extracted with an additional 200 ml
  12. washwashed successively with 90 ml
  13. dry with materialof saturated aqueous sodium bicarbonate, dried
  14. filtrationfiltered
  15. customThe organic solution is evaporated

Sources & evidence

ORD record
ord-2327def914a349baa1dc46312f028262
Source dataset
uspto-grants-1989_09
Patent number
US04870199

Reaction notes

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