3,4-dihydro-2H-pyran → HCID 57467603, compound

HRID 1662427Notes

Reaction equation

HRID 1662427 reaction equation
[Br:1][C:2]1[C:3]([OH:13])=[CH:4][C:5]([F:12])=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8].[O:14]1[CH:19]=[CH:18][CH2:17][CH2:16][CH2:15]1>C(Cl)Cl.CC1C=CC(S([O-])(=O)=O)=CC=1.C1C=C[NH+]=CC=1>[Br:1][C:2]1[C:3]([O:13][CH:15]2[CH2:16][CH2:17][CH2:18][CH2:19][O:14]2)=[CH:4][C:5]([F:12])=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8]

Participants

5

Reactant 2

HCID 80803,4-dihydro-2H-pyranHCID 574676025-Bromo-2-fluoro-4-hydroxy-benzoic acid methyl ester

Product 1

HCID 57467603HCID 57467603, compoundYield 76%

Reagents, catalysts & solvents 2

HCID 466102Benzenesulfonic acid, 4-methyl-, compd. with pyridine (1:1)CatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
50 °C

Procedure

To a round bottom containing 66.43B (13.15 g, 52.8 mmol) in dry DCM (90 mL) was added 3,4-dihydro-2H-pyran (10 mL, 110 mmol) followed by PPTS (0.13 g, 0.53 mmol). The reaction mixture was heated to a gentle reflux (50° C.) and monitored with TLC and LC-MS. After 24 hours, the reaction was concentrated under reduced pressure and then diluted with MeOH. After concentration, the residue was heated in a round bottom flask containing MeOH on the rotary evaporator (without vacuum.) at 40° C. After about 30 minutes, the solution was concentrated to a volume of about 5 mL. After cooling to room temperature, the white solid was filtered and rinsed once with MeOH to yield 66.43C (13.35 g, 76% yield). 1H NMR (400 MHz, CDCl3) δ ppm 8.25 (1H, m), 6.96 (1H, d, J=12.5 Hz), 5.56 (1H, m), 3.91 (3H, s), 3.79 (1H, td, J=11.1, 2.5 Hz), 3.65 (1H, d, J=10.6 Hz), 2.23 (2H, m), 1.96 (3H, m), 1.68 (1H, m).

Workup

  1. temperatureThe reaction mixture was heated to
  2. concentrationthe reaction was concentrated under reduced pressure
  3. additiondiluted with MeOH
  4. concentrationAfter concentration
  5. temperaturethe residue was heated in a round bottom flask
  6. additioncontaining MeOH
  7. customon the rotary evaporator (without vacuum.) at 40° C
  8. waitAfter about 30 minutes
  9. concentrationthe solution was concentrated to a volume of about 5 mL
  10. temperatureAfter cooling to room temperature
  11. filtrationthe white solid was filtered
  12. washrinsed once with MeOH

Sources & evidence

ORD record
ord-e90c3191628741b282869afb9ac1ff61
Source dataset
uspto-grants-2011_10
Patent number
US08030354B2

Reaction notes

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