3-Butyn-1-OL → HCID 59305318, compound

HRID 2241002Notes

Reaction equation

HRID 2241002 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:9](=[O:22])[C:10]([C:12]2[CH:17]=[CH:16][C:15]([O:18][CH:19]([F:21])[F:20])=[CH:14][CH:13]=2)=[O:11])[CH:5]=[CH:6][C:7]=1[F:8].[CH2:23]([OH:27])[CH2:24][C:25]#[CH:26].[Al]>C(N(CC)CC)C.C(OCC)C.[Cu](I)I.[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>[F:20][CH:19]([F:21])[O:18][C:15]1[CH:16]=[CH:17][C:12]([C:10](=[O:11])[C:9]([C:4]2[CH:5]=[CH:6][C:7]([F:8])=[C:2]([C:26]#[C:25][CH2:24][CH2:23][OH:27])[CH:3]=2)=[O:22])=[CH:13][CH:14]=1

Participants

8

Reactant 3

HCID 135663-Butyn-1-OLHCID 5359268AluminumHCID 59790308HCID 59790308, compound

Product 1

HCID 59305318HCID 59305318, compoundYield 82.4%

Reagents, catalysts & solvents 4

HCID 83717Copper iodideCatalystHCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 3283Diethyl EtherSolventHCID 8471TriethylamineSolvent

Procedure

In a 0.5-2 ml Biotage conical microwave vial equipped with magnetic spin vane was dissolved 1-(3-Bromo-4-fluoro-phenyl)-2-(4-difluoromethoxy-phenyl)-ethane-1,2-dione (100 mg, 0.268 mmol) in triethylamine (1.25 mL). Copper iodide (10 mg, 0.052 mmol) and Tetrakis(triphenylphosphine) palladium (20 mg, 0.017 mmol) were added. Lastly But-3-yn-1-ol (100 mg, 1.04 mmol) was added, the vial was covered with a teflon septa, an aluminum cap was crimped in place, and the assembly was set on a Biotage Emrys microwave instrument to irradiate at 80° C. for one hour. The crude reaction was diluted with diethylether (60 mL), washed with saturated ammonium chloride (2×30 mL) and purified via column chromatography on a Yamazen W-Prep 2XY using a two-step automatic gradient elution: 100% hexanes (4 min) to 18% EtOAc (12 min), hold 4 min then to 80% EtOAc (16 min) hold 15 minutes. The resultant oil was placed under high vacuum overnight to afford 80 mgs of beige solid (82%).

Workup

  1. customIn a 0.5-2 ml Biotage conical microwave vial equipped with magnetic spin vane
  2. customto irradiate at 80° C. for one hour
  3. customThe crude reaction
  4. washwashed with saturated ammonium chloride (2×30 mL)
  5. custompurified via column chromatography on a Yamazen W-Prep
  6. washa two-step automatic gradient elution
  7. waitto 80% EtOAc (16 min) hold 15 minutes
  8. customwas placed under high vacuum overnight

Sources & evidence

ORD record
ord-1ff5055e7ddc41cdbf72cb3e94923974
Source dataset
uspto-grants-2010_05
Patent number
US07723368B2

Reaction notes

Loading…