Phenol → 1-Acetyl-6-bromo-5-[(1,2,3,5,6,8a-hexahydroindolizin-7-yl)methoxy]indoline

HRID 1274236Notes

Reaction equation

HRID 1274236 reaction equation
[C:1]([N:4]1[C:12]2[C:7](=[CH:8][C:9]([OH:14])=[C:10]([Br:13])[CH:11]=2)[CH2:6][CH2:5]1)(=[O:3])[CH3:2].[CH2:15]1[CH:23]2[N:18]([CH2:19][CH2:20][C:21]([CH2:24]O)=[CH:22]2)[CH2:17][CH2:16]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O.C1(O)C=CC=CC=1>C1COCC1.C(OCC)(=O)C>[C:1]([N:4]1[C:12]2[C:7](=[CH:8][C:9]([O:14][CH2:24][C:21]3[CH2:20][CH2:19][N:18]4[CH:23]([CH:22]=3)[CH2:15][CH2:16][CH2:17]4)=[C:10]([Br:13])[CH:11]=2)[CH2:6][CH2:5]1)(=[O:3])[CH3:2]

Participants

8

Reactant 5

HCID 996PhenolHCID 11776Triphenylphosphine2×HCID 220568ethyl N-ethoxycarbonyliminocarbamate2×HCID 219483801-(6-Bromo-5-hydroxy-2,3-dihydro-1H-indol-1-yl)ethan-1-oneHCID 221209331,2,3,5,6,8a-Hexahydroindolizine-7-methanol

Product 1

HCID 221209261-Acetyl-6-bromo-5-[(1,2,3,5,6,8a-hexahydroindolizin-7-yl)methoxy]indolineYield 13.3%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

1-Acetyl-6-bromo-5-hydroxyindoline (Tetrahedron, 1973, 29(8), 1115) (1.24 g, 4.8 mmol), 1,2,3,5,6,8a-hexahydroindolizine-7-methanol (D2, 0.74 g, 4.8 mmol) and triphenylphosphine (1.27 g, 4.8 mmol) were stirred under Ar in dry THF (50 ml) as diethyl azodicarboxylate (0.76 ml, 4.8 mmol) was added dropwise. The mixture was stirred for 1 h, diluted with ethyl acetate, and extracted with dil. HCl. The extract was basified with potassium carbonate, and extracted with chloroform. This extract was dried (Na2SO4) and evaporated to give a dark oil. Further treatment of this oil as above with the phenol, triphenylphosphine and diethyl azodicarboxylate caused reaction to proceed further. Chromatography on silica, eluting with 0-20% methanol/dichloromethane, gave the title compound (0.25 g, 13%) as a brown gum.

Workup

  1. additionwas added dropwise
  2. extractionextracted with dil. HCl
  3. extractionextracted with chloroform
  4. dry with materialThis extract was dried (Na2SO4)
  5. customevaporated
  6. customto give a dark oil
  7. customreaction
  8. washChromatography on silica, eluting with 0-20% methanol/dichloromethane

Sources & evidence

ORD record
ord-72d97894ddc44ef3a5690cf2bd344327
Source dataset
uspto-grants-2000_12
Patent number
US06156783

Reaction notes

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