Methanol → 2-[2-(2,4-difluoro-phenyl)-2H-[1,2,4]triazol-3-yl]-4,5-dihydro-6-oxa-1-thia-benzo[e]azulene-9-carboxylic acid methyl ester

HRID 2079018Notes

Reaction equation

HRID 2079018 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]2[O:14][CH2:13][CH2:12][C:11]3[CH:10]=[C:9]([C:15]4[N:19]([C:20]5[CH:25]=[CH:24][C:23]([F:26])=[CH:22][C:21]=5[F:27])[N:18]=[CH:17][N:16]=4)[S:8][C:7]=3[C:6]=2[CH:28]=1.F[B-](F)(F)F.C(P(CCCC)CCCC)CCC.C[OH:48].N12CCCN=C1CCCCC2.C1[CH2:64][O:63][CH2:62]C1>ClCCl.[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[Mo]>[CH3:62][O:63][C:64]([C:2]1[CH:3]=[CH:4][C:5]2[O:14][CH2:13][CH2:12][C:11]3[CH:10]=[C:9]([C:15]4[N:19]([C:20]5[CH:25]=[CH:24][C:23]([F:26])=[CH:22][C:21]=5[F:27])[N:18]=[CH:17][N:16]=4)[S:8][C:7]=3[C:6]=2[CH:28]=1)=[O:48]

Participants

8

Reactant 5

HCID 887MethanolHCID 8028TetrahydrofuranHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 579004365-(9-bromo-4,5-dihydro-6-oxa-1-thia-benzo[e]azulen-2-yl)-1-(2,4-difluoro-phenyl)-1H-[1,2,4]triazoleHCID 71317416Tributyl phosphine tetrafluoroborate

Product 1

HCID 668865722-[2-(2,4-difluoro-phenyl)-2H-[1,2,4]triazol-3-yl]-4,5-dihydro-6-oxa-1-thia-benzo[e]azulene-9-carboxylic acid methyl ester

Reagents, catalysts & solvents 2

HCID 98885Molybdenum carbonyl (Mo(CO)6)CatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
130 °C

Procedure

A mixture of 5-(9-bromo-4,5-dihydro-6-oxa-1-thia-benzo[e]azulen-2-yl)-1-(2,4-difluoro-phenyl)-1H-[1,2,4]triazole (847 mg), molybdenum hexacarbonyl (485 mg), Herman's catalyst (173 mg), tributyl phosphine tetrafluoroborate (106 mg), methanol (8 ml), THF (8 ml), and 1,8-diazabicyclo[5.4.0]undec-7-ene (0.82 mL) was heated in the microwave at 130° C. for 30 minutes. The reaction mixture was cooled, and then diluted with dichloromethane, washed with water, dried (MgSO4) and the solvent removed in vacuo. Purification using flash chromatography yielded the corresponding methyl ester, 2-[2-(2,4-difluoro-phenyl)-2H-[1,2,4]triazol-3-yl]-4,5-dihydro-6-oxa-1-thia-benzo[e]azulene-9-carboxylic acid methyl ester. Standard hydrolysis using sodium hydroxide in methanol/THF/water yielded the corresponding carboxylic acid, 2-[2-(2,4-difluoro-phenyl)-2H-[1,2,4]triazol-3-yl]-4,5-dihydro-6-oxa-1-thia-benzo[e]azulene-9-carboxylic acid.

Workup

  1. temperatureThe reaction mixture was cooled
  2. washwashed with water
  3. dry with materialdried (MgSO4)
  4. customthe solvent removed in vacuo
  5. customPurification

Sources & evidence

ORD record
ord-94cd7ef3da5643e786cafc865206db72
Source dataset
uspto-grants-2011_04
Patent number
US07928248B2

Reaction notes

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