Potassium Carbonate → HCID 71271322, compound

HRID 1525854Notes

Reaction equation

HRID 1525854 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([CH:8]([N:14]2[CH2:28][CH2:27][C:17]3([O:22][CH2:21][C:20](=[O:23])[N:19]([CH:24]4[CH2:26][CH2:25]4)[CH2:18]3)[CH2:16][CH2:15]2)[CH2:9][C:10]([O:12][CH3:13])=[O:11])=[CH:4][CH:3]=1.CC1(C)C(C)(C)OB([C:37]2[CH:46]=[C:45]3[C:40]([CH:41]=[CH:42][CH:43]=[N:44]3)=[CH:39][CH:38]=2)O1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl>[CH:24]1([N:19]2[CH2:18][C:17]3([CH2:27][CH2:28][N:14]([CH:8]([C:5]4[CH:6]=[CH:7][C:2]([C:37]5[CH:46]=[C:45]6[C:40]([CH:41]=[CH:42][CH:43]=[N:44]6)=[CH:39][CH:38]=5)=[CH:3][CH:4]=4)[CH2:9][C:10]([O:12][CH3:13])=[O:11])[CH2:15][CH2:16]3)[O:22][CH2:21][C:20]2=[O:23])[CH2:26][CH2:25]1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 592961167-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)QuinolineHCID 71270889Methyl 3-(4-bromophenyl)-3-(4-cyclopropyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)propanoate

Product 1

HCID 71271322HCID 71271322, compound

Reagents, catalysts & solvents 3

HCID 178418807HCID 178418807, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of methyl 3-(4-bromophenyl)-3-(4-cyclopropyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)propanoate (0.399 mmol) in 1,4-dioxane (2 mL) was treated with 7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinoline (0.439 mmol), PdCl2(dppf)-CH2Cl2 adduct (0.020 mmol) and 2M aq potassium carbonate (1.196 mmol). The reaction vessel was purged with nitrogen and the reaction irradiated in a Biotage Initiator microwave at 120° C. for 15 minutes. The black reaction mixture was then diluted with water (50 mL) and extracted with dichloromethane three times. The combined organic layer was treated with Silicycle Si-thiol (30 mg), dried over sodium sulfate, filtered and concentrated in vacuo. Purification of the residue by reverse phase HPLC (15-60% acetonitrile/water with 0.1% NH4OH) afforded the title compound as a yellow oil, which was subsequently lyophilized from 1 mL of water and then triturated with hexanes and dried under a nitrogen stream to afford the title compound as a white solid (61%). MS(ES)+ m/e 500.3 [M+H]+.

Workup

  1. customThe reaction vessel was purged with nitrogen
  2. customthe reaction irradiated in a Biotage Initiator microwave at 120° C. for 15 minutes
  3. customThe black reaction mixture
  4. extractionextracted with dichloromethane three times
  5. additionThe combined organic layer was treated with Silicycle Si-thiol (30 mg)
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customPurification of the residue by reverse phase HPLC (15-60% acetonitrile/water with 0.1% NH4OH)

Sources & evidence

ORD record
ord-703456e1ce9b4e7aab24b26736def1b0
Source dataset
uspto-grants-2015_07
Patent number
US09084794B2

Reaction notes

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