Diisopropylamine → benzyl (2S*,3R*)-5-(tert-butyldiphenylsilanyloxy)-3-hydroxy-2-(3,4,5-trifluorophenyl)pentanoate

HRID 546684Notes

Reaction equation

HRID 546684 reaction equation
C([Li])CCC.C(NC(C)C)(C)C.[F:13][C:14]1[CH:15]=[C:16]([CH2:22][C:23]([O:25][CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)=[O:24])[CH:17]=[C:18]([F:21])[C:19]=1[F:20].[O:33]([CH2:51][CH2:52][CH2:53][OH:54])[Si:34]([C:47]([CH3:50])([CH3:49])[CH3:48])([C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1)[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1.[Cl-].[NH4+]>C1COCC1.C(OCC)(=O)C>[Si:34]([O:33][CH2:51][CH2:52][C@@H:53]([OH:54])[C@H:22]([C:16]1[CH:15]=[C:14]([F:13])[C:19]([F:20])=[C:18]([F:21])[CH:17]=1)[C:23]([O:25][CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)=[O:24])([C:47]([CH3:49])([CH3:50])[CH3:48])([C:41]1[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=1)[C:35]1[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=1.[Si:34]([O:33][CH2:51][CH2:52][C@H:53]([OH:54])[C@H:22]([C:16]1[CH:15]=[C:14]([F:13])[C:19]([F:20])=[C:18]([F:21])[CH:17]=1)[C:23]([O:25][CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)=[O:24])([C:47]([CH3:49])([CH3:50])[CH3:48])([C:41]1[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=1)[C:35]1[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=1

Participants

9

Reactant 5

HCID 7912DiisopropylamineHCID 25517Ammonium ChlorideHCID 102451343-(Tert-butyldiphenylsiloxy)propanolHCID 86628508Benzyl (3,4,5-trifluorophenyl)acetateHCID 178418339Butyllithium

Product 2

HCID 66838983benzyl (2S*,3R*)-5-(tert-butyldiphenylsilanyloxy)-3-hydroxy-2-(3,4,5-trifluorophenyl)pentanoateHCID 66839318benzyl (2S*,3S*)-5-(tert-butyldiphenylsilanyloxy)-3-hydroxy-2-(3,4,5-trifluorophenyl)pentanoate

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent3×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

n-Butyl lithium (1.82 mL; 2.66 M solution in hexane) was added dropwise to a solution of diisopropylamine (0.735 mL) in THF (6 mL) at 0° C. The reaction solution was stirred at 0° C. for 20 minutes and then cooled to −78° C. Benzyl (3,4,5-trifluorophenyl)acetate (1.13 g) in THF (18 mL) was added dropwise to the reaction solution, and the reaction solution was stirred at −78° C. for 15 minutes. Thereafter, 3-(tert-butyldiphenylsiloxy)propanol (CAS No. 112897-03-7, 1.26 g) in THF (6 mL) was added dropwise to the reaction solution, and the reaction solution was stirred at −78° C. for 30 minutes. A saturated ammonium chloride solution was added to the reaction solution, and the reaction solution was returned to room temperature. Ethyl acetate was added and the organic layer was separated. The resulting organic layer was washed with brine, dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (elution solvent: heptane-ethyl acetate system) to obtain 840 mg of benzyl (2S*,3R*)-5-(tert-butyldiphenylsilanyloxy)-3-hydroxy-2-(3,4,5-trifluorophenyl)pentanoate and 765 mg of benzyl (2S*,3S*)-5-(tert-butyldiphenylsilanyloxy)-3-hydroxy-2-(3,4,5-trifluorophenyl)pentanoate.

Workup

  1. temperaturecooled to −78° C
  2. stirringthe reaction solution was stirred at −78° C. for 15 minutes
  3. stirringthe reaction solution was stirred at −78° C. for 30 minutes
  4. customwas returned to room temperature
  5. customthe organic layer was separated
  6. washThe resulting organic layer was washed with brine
  7. dry with materialdried over anhydrous magnesium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by silica gel column chromatography (elution solvent: heptane-ethyl acetate system)

Sources & evidence

ORD record
ord-5341a4c9430947c08ea7dd838ffcb6a4
Source dataset
uspto-grants-2011_05
Patent number
US07935815B2

Reaction notes

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