4-Pentyn-1-ol → [4-(5-Hydroxy-pent-1-ynyl)-phenyl]-methyl-carbamic acid tert-butyl ester

HRID 1841604Notes

Reaction equation

HRID 1841604 reaction equation
[C:1]([O:5][C:6](=[O:16])[N:7]([C:9]1[CH:14]=[CH:13][C:12](I)=[CH:11][CH:10]=1)[CH3:8])([CH3:4])([CH3:3])[CH3:2].[CH2:17]([OH:22])[CH2:18][CH2:19][C:20]#[CH:21]>N1CCCCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:1]([O:5][C:6](=[O:16])[N:7]([C:9]1[CH:14]=[CH:13][C:12]([C:21]#[C:20][CH2:19][CH2:18][CH2:17][OH:22])=[CH:11][CH:10]=1)[CH3:8])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 2

HCID 793464-Pentyn-1-ol2×HCID 18537740N-Boc 4-Iodo-N-methylaniline

Product 1

HCID 68615769[4-(5-Hydroxy-pent-1-ynyl)-phenyl]-methyl-carbamic acid tert-butyl esterYield 115.8%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8082PiperidineSolvent

Conditions

Temperature
45 °C

Procedure

The synthesis was performed following a procedure of 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. A solution of 4.45 g (12.5 mmol) of (4-Iodo-phenyl)-methyl-carbamic acid tert-butyl ester in 25 ml piperidine was degassed (argon) and treated with 722 mg (0.625 mmol) Pd(PPh3)4 and 119 mg (0.625 mmol) Cul. The reaction mixture was stirred at 45° C. for 10 min and then slowly (45 min) heated to 80° C. while adding 0.9 ml (9.4 mmol) of 4-pentin-1-ol. At 80° C. a second portion of 0.9 ml (9.4 mmol) 4-pentin-1-ol was added during 45 min. The reaction mixture was stirred at this temperature for 2 h and then extracted with chilled water acidified with KHSO4/Et2O (3×). The organic phases were washed with aqueous 10% NaCl, dried (Na2SO4) and evaporated. Purification by flash-chromatography on silica gel (CH2Cl2/EtOAc 95:5) yielded 3.15 g (87%) of [4-(5-Hydroxy-pent-1-ynyl)-phenyl]-methyl-carbamic acid tert-butyl ester, mp: 103-105° C.; MS: 289 (M).

Workup

  1. customCollect
  2. temperatureslowly (45 min) heated to 80° C.
  3. stirringThe reaction mixture was stirred at this temperature for 2 h
  4. extractionextracted with chilled water
  5. washThe organic phases were washed with aqueous 10% NaCl
  6. dry with materialdried (Na2SO4)
  7. customevaporated
  8. customPurification by flash-chromatography on silica gel (CH2Cl2/EtOAc 95:5)

Sources & evidence

ORD record
ord-9409905deca64b29a0dde532ebbb2940
Source dataset
uspto-grants-2004_01
Patent number
US06683201B2

Reaction notes

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