Dichloromethane → HCID 178498769, compound

HRID 2404142Notes

Reaction equation

HRID 2404142 reaction equation
[C:1]([C@H:5]1[CH2:10][CH2:9][C@H:8]([O:11][C:12]2[C:13](I)=[C:14]3[C:19](=[CH:20][CH:21]=2)[CH:18]=[C:17]([CH2:22][N:23]2[CH2:26][CH:25]([C:27]([O:29][CH3:30])=[O:28])[CH2:24]2)[CH:16]=[CH:15]3)[CH2:7][CH2:6]1)([CH3:4])([CH3:3])[CH3:2].[CH3:32]B(O)O.C([O-])([O-])=O.[K+].[K+].ClCCl>>[C:1]([C@H:5]1[CH2:10][CH2:9][C@H:8]([O:11][C:12]2[C:13]([CH3:32])=[C:14]3[C:19](=[CH:20][CH:21]=2)[CH:18]=[C:17]([CH2:22][N:23]2[CH2:26][CH:25]([C:27]([O:29][CH3:30])=[O:28])[CH2:24]2)[CH:16]=[CH:15]3)[CH2:7][CH2:6]1)([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 139377Methylboronic AcidHCID 178498774HCID 178498774, compound

Product 1

HCID 178498769HCID 178498769, compoundYield 33.7%

Conditions

Temperature
90 °C

Procedure

A flask charged with compound methyl 1-((6-((trans)-4-tert-butylcyclohexyloxy)-5-iodonaphthalen-2-yl)methyl)azetidine-3-carboxylate (300 mg, 0.56 mmol), methylboronic acid (66 mg, 1.1 mmol, 2.0 eq), 2 M aq K2CO3 (5 mL, 3.0 equiv) and [1,1-bis(diphenylphosphino) ferroene]dichloropalladium (II) complex with dichloromethane (1:1) (45 mg, 0.05 mmol, 0.1 equiv) was flushed with nitrogen. 1,4-Dioxane (20 mL) was added and the reaction was stirred at 90° C. for 5 h. The solution was cooled to room temperature. The solvent was removed and the residue was purified by column chromatography (PE/EA=1:1) to give compound the title compound as a white solid (80 mg, 33%). ESI-MS (M+H+): 424.3. 1H NMR (400 MHz, CDCl3) δ: 7.88 (d, 1H), 7.64-7.61 (m, 2H), 7.40 (dd, 1H), 7.23 (d, 1H), 4.10-4.08 (m, 1H), 3.79 (s, 2H), 3.74 (s, 3H), 3.59-3.56 (m, 2H), 3.39-3.36 (m, 3H), 2.53 (s, 3H), 2.20-2.17 (m, 2H), 1.86-1.83 (m, 2H), 1.48-1.43 (m, 2H), 1.10-1.26 (m, 3H), 0.86 (s, 9H)

Workup

  1. customwas flushed with nitrogen
  2. addition1,4-Dioxane (20 mL) was added
  3. temperatureThe solution was cooled to room temperature
  4. customThe solvent was removed
  5. customthe residue was purified by column chromatography (PE/EA=1:1)

Sources & evidence

ORD record
ord-06126509b9ba49ca95086307dd6edd08
Source dataset
uspto-grants-2014_08
Patent number
US08802659B2

Reaction notes

Loading…