Tris(1,1-dimethylethyl)phosphine → HCID 59807032, compound

HRID 1922472Notes

Reaction equation

HRID 1922472 reaction equation
P(C(C)(C)C)(C(C)(C)C)C(C)(C)C.Br[C:15]1[CH:16]=[C:17]2[C:21](=[CH:22][CH:23]=1)[N:20]([CH:24]1[CH2:29][CH2:28][N:27]([C:30](OC(C)(C)C)=O)[CH2:26]C1)[CH2:19][CH2:18]2.[Li+].C[Si]([N-:42][Si](C)(C)C)(C)C>C1COCC1.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]>[CH3:30][N:27]1[CH2:28][CH2:29][CH:24]([N:20]2[C:21]3[C:17](=[CH:16][C:15]([NH2:42])=[CH:23][CH:22]=3)[CH2:18][CH2:19]2)[CH2:26]1

Participants

6

Reactant 3

HCID 83681Tris(1,1-dimethylethyl)phosphineHCID 2733832Lithium HexamethyldisilazideHCID 22029161tert-Butyl 4-(5-bromo-2,3-dihydro-1H-indol-1-yl)piperidine-1-carboxylate

Product 1

HCID 59807032HCID 59807032, compoundYield 104.8%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
100 °C

Procedure

A solution of Pd2(dba)3 (0.08 g, 0.087 mmol) in dry THF (5 mL) was treated with PtBu3 (1.06 mL, 0.351 mmol, 10% in hexanes), followed by compound 3 (0.67 g, 1.757 mmol) in dry THF (5 mL) and LiHMDS (3.51 mL, 3.514 mmol) at room temperature. The resulting mixture was stirred at 100° C. in a seal tube for 3 h. The reaction was brought to room temperature and quenched with TBAF (5 mL, 1 M solution in THF). After stirring for 15 min., solution was basified with 1 N NaOH solution (50 mL) and product was extracted into CH2Cl2 (3×20 mL). The combined CH2Cl2 layer was dried (Na2SO4) and evaporated to obtain the crude product. The crude was purified by column chromatography (2 M NH3 in MeOH:CH2Cl2, 2.5:97.5) to obtain compound 4 (0.4 g, 72%) as a foam.

Workup

  1. customwas brought to room temperature
  2. customquenched with TBAF (5 mL, 1 M solution in THF)
  3. stirringAfter stirring for 15 min.
  4. extractionwas extracted into CH2Cl2 (3×20 mL)
  5. dry with materialThe combined CH2Cl2 layer was dried (Na2SO4)
  6. customevaporated
  7. customto obtain the crude product
  8. customThe crude was purified by column chromatography (2 M NH3 in MeOH:CH2Cl2, 2.5:97.5)

Sources & evidence

ORD record
ord-3defb879195d4271a53df15df698a88b
Source dataset
uspto-grants-2012_05
Patent number
US08173813B2

Reaction notes

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