Nitrogen → HCID 86635714, compound

HRID 1039732Notes

Reaction equation

HRID 1039732 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH2:8][C@H:9]([NH:21][C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])[C@H:10]([O:13][Si:14]([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15])[CH2:11][OH:12])[CH:5]=[CH:6][CH:7]=1.N#N.F[B-](F)(F)F.C([PH+](C(C)(C)C)C(C)(C)C)(C)(C)C.[C:49]([Si:51]([CH3:54])([CH3:53])[CH3:52])#[CH:50].C(NC(C)C)(C)C>CCOC(C)=O.C1C=CC(C#N)=CC=1.C1C=CC(C#N)=CC=1.Cl[Pd]Cl.[Cu](I)I.C(Cl)Cl>[Si:14]([O:13][C@H:10]([CH2:11][OH:12])[C@@H:9]([NH:21][C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])[CH2:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([C:50]#[C:49][Si:51]([CH3:54])([CH3:53])[CH3:52])[CH:3]=1)([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15]

Participants

10

Reactant 5

HCID 947NitrogenHCID 7912DiisopropylamineHCID 66111TrimethylsilylacetyleneHCID 2734635Tri-tert-butylphosphine tetrafluoroborateHCID 71494143HCID 71494143, compound

Product 1

HCID 86635714HCID 86635714, compound

Reagents, catalysts & solvents 4

HCID 83717Copper iodideCatalystHCID 498840Bis(benzonitrile)palladium chlorideCatalystHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

Tert-Butyl (2S,3S)-1-(3-bromophenyl)-3-(tert-butyldimethylsilyloxy)-4-hydroxybutan-2-ylcarbamate (2.09 g, 4.40 mmol) was concentrated under reduced pressure from DCM in a 50-mL RBF. The flask was filled with N2 (g), then PdCl2(PhCN)2 (0.101 g, 0.264 mmol), tri-tert-butylphosphonium tetrafluoroborate (0.153 g, 0.529 mmol), and copper iodide (33.6 mg, 0.176 mmol) were added. The flask was evacuated and refilled with N2 (g). This process was repeated 3×, then a rubber septum was attached. Ar (g)-degassed dioxane (10 mL) was added, and the flask was sonicated for 5 min to dissolve the starting materials. Ethynyltrimethylsilane (0.915 ml, 6.61 mmol) and diisopropylamine (0.942 ml, 6.61 mmol) were added in sequence, and the resulting black solution was stirred at RT for 4 h. The reaction mixture was diluted with EtOAc and filtered through a pad of celite. The filtrate was evaporated, and the crude product was purified by chromatography on a 120-g Redi-Sep silica gel column, eluting with 5-40% ethyl acetate/hexanes to give tert-butyl (2S,3S)-3-(tert-butyldimethylsilyloxy)-4-hydroxy-1-(3-(2-(trimethylsilyl)ethynyl)phenyl)butan-2-ylcarbamate as a brown oil.

Workup

  1. customThe flask was evacuated
  2. additionrefilled with N2 (g)
  3. additionAr (g)-degassed dioxane (10 mL) was added
  4. customthe flask was sonicated for 5 min
  5. dissolutionto dissolve the starting materials
  6. filtrationfiltered through a pad of celite
  7. customThe filtrate was evaporated
  8. customthe crude product was purified by chromatography on a 120-g Redi-Sep silica gel column
  9. washeluting with 5-40% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-d1f35d871c18473c88b838797b32e454
Source dataset
uspto-grants-2013_10
Patent number
US08552181B2

Reaction notes

Loading…