Methanol → HCID 89816222, compound

HRID 525364Notes

Reaction equation

HRID 525364 reaction equation
[C:1]1([CH:7]2[C:11]3([CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]3)[O:10][C:9](=[O:17])[NH:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.I[C:19]1[CH:37]=[CH:36][C:22]([C:23]([NH:25][C:26]2[CH:27]=[CH:28][CH:29]=[C:30]3[C:35]=2[N:34]=[CH:33][CH:32]=[CH:31]3)=[O:24])=[CH:21][CH:20]=1.C(=O)([O-])[O-].[K+].[K+].CO>CN(C=O)C.C(Cl)Cl.[Cu]I>[O:17]=[C:9]1[N:8]([C:19]2[CH:37]=[CH:36][C:22]([C:23]([NH:25][C:26]3[CH:27]=[CH:28][CH:29]=[C:30]4[C:35]=3[N:34]=[CH:33][CH:32]=[CH:31]4)=[O:24])=[CH:21][CH:20]=2)[CH:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[C:11]2([CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]2)[O:10]1

Participants

8

Reactant 4

HCID 887MethanolHCID 11430Potassium CarbonateHCID 12885306HCID 12885306, compoundHCID 41661718HCID 41661718, compound

Product 1

HCID 89816222HCID 89816222, compoundYield 11%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
120 °C

Procedure

To a 50 mL dried round bottom flask containing a degassed solution of 4-phenyl-1-oxa-3-azaspiro[4.5]decan-2-one (1 eq., 1.73 mmol) and 4-iodo-N-(quinolin-8-yl)benzamide (1.2 eq.) in DMF (15 mL), potassium carbonate (2.5 eq.) and trans (N,N)-dimethyl cyclohexanediamine (0.5 eq.), was added CuI (0.1 eq). The resulting mixture was then stirred at 120° C. for 15 hours. Reaction progress was monitored by TLC (TLC eluent: 10% MeOH in DCM). The reaction mixture was cooled and poured into crushed ice (5 g). The solid thus obtained was filtered, washed with water (25 mL) and dissolved in DCM. The DCM solution was then washed with water (100 mL), brine (50 mL) and dried over anhydrous Na2SO4, filtered, concentrated and purified by column chromatography using silica gel and DCM as eluting solvent to yield (R+S) 4-(2-oxo-4-phenyl-1-oxa-3-azaspiro[4.5]decan-3-yl)-N-(quinolin-8-yl)benzamide (90 mg, 11%) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ: 10.46 (s, 1H), 8.95 (dd, J=4.4, 1.6 Hz, 1H), 8.66 (d, J=6.4 Hz, 1H), 8.44 (dd, J=8.4, 1.6 Hz, 1H), 7.94 (d, J=8.0 Hz, 2H), 7.75-7.72 (m, 3H), 7.68-7.61 (m, 3H), 7.32-7.39 (m, 4H), 5.52 (s, 1H), 2.08-2.11 (m, 1H), 1.83-1.89 (m, 1H), 1.74-1.53 (m, 3H), 1.35-1.42 (m, 2H), 1.20-1.23 (m, 3H). m/z (ESI) 478.2 (M+H)+.

Workup

  1. customTo a 50 mL dried round bottom flask
  2. customReaction progress
  3. temperatureThe reaction mixture was cooled
  4. additionpoured
  5. customThe solid thus obtained
  6. filtrationwas filtered
  7. washwashed with water (25 mL)
  8. dissolutiondissolved in DCM
  9. washThe DCM solution was then washed with water (100 mL), brine (50 mL)
  10. dry with materialdried over anhydrous Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated
  13. custompurified by column chromatography
  14. washas eluting solvent

Sources & evidence

ORD record
ord-6b4e9a5cab0e4c3d8c6f7525bee51985
Source dataset
uspto-grants-2016_05
Patent number
US09340549B2

Reaction notes

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