Lithium Hexamethyldisilazide → tert-butyl [(4'R)-6'-amino-2',2'-dimethyldispiro[cyclopropane-1,3'-chromene-4',4''-[1,3]oxazol]-2''-yl]carbamate

HRID 594880Notes

Reaction equation

HRID 594880 reaction equation
[C:1]([O:5][C:6]([N:8]([C:16]1[O:17][CH2:18][C@@:19]2([C:29]3[C:24](=[CH:25][CH:26]=[C:27](Br)[CH:28]=3)[O:23][C:22]([CH3:32])([CH3:31])[C:21]32[CH2:34][CH2:33]3)[N:20]=1)C(OC(C)(C)C)=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].F[B-](F)(F)F.C([PH+](C(C)(C)C)C(C)(C)C)(C)(C)C.C[Si]([N-:57][Si](C)(C)C)(C)C.[Li+]>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]>[C:1]([O:5][C:6](=[O:7])[NH:8][C:16]1[O:17][CH2:18][C@@:19]2([C:29]3[C:24](=[CH:25][CH:26]=[C:27]([NH2:57])[CH:28]=3)[O:23][C:22]([CH3:32])([CH3:31])[C:21]32[CH2:34][CH2:33]3)[N:20]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 2733832Lithium HexamethyldisilazideHCID 2734635Tri-tert-butylphosphine tetrafluoroborateHCID 86724275di-tert-butyl [(4'R)-6'-bromo-2',2'-dimethyldispiro[cyclopropane-1,3'-chromene-4',4''-[1,3]oxazol]-2''-yl]imidodicarbonate

Product 1

HCID 86724280tert-butyl [(4'R)-6'-amino-2',2'-dimethyldispiro[cyclopropane-1,3'-chromene-4',4''-[1,3]oxazol]-2''-yl]carbamateYield 99.7%

Reagents, catalysts & solvents 1

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladiumCatalyst

Conditions

Temperature
60 °C

Procedure

To a mixture of di-tert-butyl[(4′R)-6′-bromo-2′,2′-dimethyldispiro[cyclopropane-1,3′-chromene-4′,4″-[1,3]oxazol]-2″-yl]imidodicarbonate (1.98 g, 3.68 mmol), bis(dibenzylideneacetone)palladium(0) (212 mg, 0.369 mmol), and tri-tert-butylphosphonium tetrafluoroborate (108 mg, 0.371 mmol) was added lithium bis(trimethylsilyl)amide (1M solution in toluene, 18 ml, 18 mmol) at room temperature under argon atmosphere. The mixture was stirred at 60° C. for 2 hours and then quenched with saturated aqueous ammonium chloride. The mixture was extracted with chloroform. The organic layer was dried over anhydrous magnesium sulfate, and concentrated in vacuo. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=100:0-50:50-0:100) to afford tert-butyl[(4′R)-6′-amino-2′,2′-dimethyldispiro[cyclopropane-1,3′-chromene-4′,4″-[1,3]oxazol]-2″-yl]carbamate (1.37 g).

Workup

  1. customquenched with saturated aqueous ammonium chloride
  2. extractionThe mixture was extracted with chloroform
  3. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate=100:0-50:50-0:100)

Sources & evidence

ORD record
ord-f236d44accf743bc8d9743bc40ea7339
Source dataset
uspto-grants-2016_01
Patent number
US09242973B2

Reaction notes

Loading…