Lithium Hexamethyldisilazide → HCID 86730036, compound

HRID 2199467Notes

Reaction equation

HRID 2199467 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C@H:8]2[CH2:17][CH2:16][C@@:10]3([NH:14][C:13](=[O:15])[O:12][CH2:11]3)[CH2:9]2)=[CH:4][CH:3]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[Cl-].[C:29]([O:33][C:34](=[O:37])[CH2:35][Zn+])([CH3:32])([CH3:31])[CH3:30]>O1CCOCC1.C(OCC)(=O)C.C1([C-]2C(C3C=CC=CC=3)=C(C3C=CC=CC=3)C(C3C=CC=CC=3)=C2C2C=CC=CC=2)C=CC=CC=1.C(P(C(C)(C)C)[C-]1C=CC=C1)(C)(C)C.[Fe+2].C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[O:15]=[C:13]1[O:12][CH2:11][C@:10]2([CH2:16][CH2:17][C@H:8]([C:5]3[CH:6]=[CH:7][C:2]([CH2:35][C:34]([O:33][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:37])=[CH:3][CH:4]=3)[CH2:9]2)[NH:14]1

Participants

8

Reactant 3

HCID 2733832Lithium HexamethyldisilazideHCID 86730034HCID 86730034, compoundHCID 178451183HCID 178451183, compound

Product 1

HCID 86730036HCID 86730036, compoundYield 84.8%

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 129828017Ditert-butyl(cyclopenta-2,4-dien-1-yl)phosphane;iron(2+);(2,3,4,5-tetraphenylcyclopenta-1,4-dien-1-yl)benzeneCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

To a mixture of (5R,7S)-7-(4-bromophenyl)-3-oxa-1-azaspiro[4.4]nonan-2-one (I-3, 1 g, 3.38 mmol) in dioxane (10 mL) at room temperature was added lithium bis(trimethylsilyl)amide (3.71 mL, 3.71 mmol). The mixture was stirred for 30 minutes, then 1,2,3,4,5-pentaphenyl-1′-(di-t-butylphosphino)ferrocene (0.121 g, 0.169 mmol), Pd2(dba)3 (0.155 g, 0.169 mmol) and (2-(tert-butoxy)-2-oxoethyl)zinc(II) chloride (8.10 mL, 4.05 mmol) were added. The reaction mixture was heated at 80° C. for 2 hours, then cooled to room temperature, diluted with ethyl acetate and washed with 1M HCl. The organic layer was dried with MgSO4, filtered and concentrated. The crude material was purified on a silica gel cartridge (40 g) using an EtOAc/hexane gradient (0-100% EtOAc over 20 minutes) to afford 950 mg of tert-butyl 2-(4-((5R,7S)-2-oxo-3-oxa-1-azaspiro[4.4]nonan-7-yl)phenyl)acetate. HPLC retention time=0.93 min (Condition G); LC/MS M+1=332.

Workup

  1. temperaturecooled to room temperature
  2. washwashed with 1M HCl
  3. dry with materialThe organic layer was dried with MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude material was purified on a silica gel cartridge (40 g)
  7. customan EtOAc/hexane gradient (0-100% EtOAc over 20 minutes)

Sources & evidence

ORD record
ord-8ba0af97ca514ee492f076c975d4c710
Source dataset
uspto-grants-2016_06
Patent number
US09359286B2

Reaction notes

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