Hydrochloric Acid → 5-(5-Hydroxy-pent-1-ynyl)-2,3-dihydro-indole-1-carboxylic acid tert-butyl ester

HRID 1633680Notes

Reaction equation

HRID 1633680 reaction equation
[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][C:13](Br)=[CH:14][CH:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:18]([OH:23])[CH2:19][CH2:20][C:21]#[CH:22].Cl>N1CCCCC1.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Cu]I>[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([C:22]#[C:21][CH2:20][CH2:19][CH2:18][OH:23])=[CH:14][CH:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 793464-Pentyn-1-ol2×HCID 21865438tert-butyl 5-bromo-2,3-dihydro-1H-indole-1-carboxylate

Product 1

HCID 695147945-(5-Hydroxy-pent-1-ynyl)-2,3-dihydro-indole-1-carboxylic acid tert-butyl esterYield 105.9%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 8082PiperidineSolvent

Procedure

To 3.73 g (12.5 mmol) 5-Bromo-2,3-dihydro-indole-1-carboxylic acid tert-butyl ester in 25 ml piperidine were added 722 mg (0.63 mmol) tetrakis-(triphenylphosphine)-palladium and 120 mg (0.625 mmol) CuI. The solution was purged with argon, and was heated to 80° C. over a period of 45 min, during which 0.9 ml (9.4 mmol) 4-pentyn-1-ol were added. Additional 0.9 ml (9.4 mmol) 4-pentyn-1-ol were added and the mixture was stirred for 2 h, poured on ice water and 2M HCl was added. The inorganic phase was extracted with ether, the combined organic phases were washed with water and dried over Na2SO4. Purification on silica gel with hexane/EtOAc 4:1 to 2:1 yielded 3.0 g (79%) 5-(5-Hydroxy-pent-1-ynyl)-2,3-dihydro-indole-1-carboxylic acid tert-butyl ester as light brown solid, MS: 302 (MH+). (See also: Stara, Irena G.; Stary, Ivo; Kollarovic, Adrian; Teply, Filip; Saman, David; Fiedler, Pavel. Coupling reactions of halobenzenes with alkynes. The synthesis of phenylacetylenes and symmetrical or unsymmetrical 1,2-diphenylacetylenes. Collect. Czech. Chem. Commun. (1999), 64(4), 649-672)

Workup

  1. customThe solution was purged with argon
  2. additionwere added
  3. additionwas added
  4. extractionThe inorganic phase was extracted with ether
  5. washthe combined organic phases were washed with water
  6. dry with materialdried over Na2SO4
  7. customPurification on silica gel with hexane/EtOAc 4:1 to 2:1

Sources & evidence

ORD record
ord-21e3c22fb55f44d8b070c7050f71189a
Source dataset
uspto-grants-2003_01
Patent number
US06503907B2

Reaction notes

Loading…