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

HRID 2212539Notes

Reaction equation

HRID 2212539 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].N1CCCCC1.[CH2:24]([OH:29])[CH2:25][CH2:26][C:27]#[CH:28].Cl>[Cu]I>[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([C:28]#[C:27][CH2:26][CH2:25][CH2:24][OH:29])=[CH:14][CH:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 8082PiperidineHCID 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 1

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)Catalyst

Procedure

To 3.73 g (12.5 mmol) 5-Bromo-2,3-dihydro-indole-1-carboxylic acid tert-butyl ester in 25 ml piperidine 722 mg (0.63 mmol) tetrakis-(triphenylphosphine)-palladium and 120 mg (0.625 mmol) CuI were added. 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-pentynol were added. Additional 0.9 ml (9.4 mmol) 4-pentynol were added and the mixture was stirred for 2 h, poured into 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-4a00153d635b4243b09bda64de80984a
Source dataset
uspto-grants-2006_09
Patent number
US07102007B2

Reaction notes

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