Triethylamine → HCID 66970922, compound

HRID 1361521Notes

Reaction equation

HRID 1361521 reaction equation
Cl.[C@@H:2]12[CH2:8][C@@H:5]([CH2:6][CH2:7]1)[CH2:4][C@H:3]2[N:9]1[CH2:14][CH2:13][CH:12]([C:15]2[CH:20]=[C:19](Br)[CH:18]=[CH:17][C:16]=2[O:22][CH3:23])[CH2:11][CH2:10]1.[C:24]1([C:30]#[CH:31])[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.C(N(CC)CC)C>C(#N)C.[Cu](I)I>[C@@H:2]12[CH2:8][C@@H:5]([CH2:6][CH2:7]1)[CH2:4][C@H:3]2[N:9]1[CH2:14][CH2:13][CH:12]([C:15]2[CH:20]=[C:19]([C:31]#[C:30][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[CH:18]=[CH:17][C:16]=2[O:22][CH3:23])[CH2:11][CH2:10]1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 10821PhenylacetyleneHCID 66970673HCID 66970673, compound

Product 1

HCID 66970922HCID 66970922, compound

Reagents, catalysts & solvents 2

HCID 83717Copper iodideCatalystHCID 6342AcetonitrileSolvent

Procedure

1-((1S,2R,4R)-bicyclo[2.2.1]heptan-2-yl)-4-(5-bromo-2-methoxyphenyl) piperidine hydrochloride (compound no. 187) (60 mg, 0.15 mmol), trans-dichlorobis(triphenylphosphine) palladium (II) (11 mg, 0.015 mmol) and copper iodide (6 mg, 0.030 mmol) were suspended in anhydrous acetonitrile (500 μL) in a microwave vial and treated with phenylacetylene (77 mg, 0.75 mmol), followed by triethylamine (250 μL). The vial was flushed with nitrogen, capped and microwaved at 140° C. for 20 min. The reaction was diluted with methanol (750 μL), filtered (Whatman 0.20 μm PTFE) and subjected to reverse-phase HPLC purification (5-50% CH3CN/0.08% TFA) to yield 1-((1S,2R,4R)-bicyclo[2.2.1]heptan-2-yl)-4-(2-methoxy-5-(phenyl-ethynyl)phenyl)piperidine (compound no. 64) as the TFA salt. LC/MS (RP-C18, 10-99% CH3CN/0.05% TFA gradient over 5 min) m/z 386.2 [M+H]+, retention time 2.86 min.

Workup

  1. customThe vial was flushed with nitrogen
  2. customcapped
  3. custommicrowaved at 140° C. for 20 min
  4. additionThe reaction was diluted with methanol (750 μL)
  5. filtrationfiltered (Whatman 0.20 μm PTFE)
  6. customsubjected to reverse-phase HPLC purification (5-50% CH3CN/0.08% TFA)

Sources & evidence

ORD record
ord-5a80ca19063c4c1cb1c1a4ae99b09be1
Source dataset
uspto-grants-2011_02
Patent number
US07880007B2

Reaction notes

Loading…