Methanol → HCID 58497930, compound

HRID 1505256Notes

Reaction equation

HRID 1505256 reaction equation
Br[C:2]1[C:10]2[O:9][C:8]([CH3:11])=[N:7][C:6]=2[C:5]([C:12]2[CH2:16][C:15]([C:21]3[CH:26]=[C:25]([Cl:27])[CH:24]=[C:23]([Cl:28])[CH:22]=3)([C:17]([F:20])([F:19])[F:18])[O:14][N:13]=2)=[CH:4][CH:3]=1.C(N(CC)CC)C.[CH3:36][OH:37].[C]=O.CN(C)[CH:42]=[O:43]>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]>[CH3:36][O:37][C:42]([C:2]1[C:10]2[O:9][C:8]([CH3:11])=[N:7][C:6]=2[C:5]([C:12]2[CH2:16][C:15]([C:21]3[CH:22]=[C:23]([Cl:28])[CH:24]=[C:25]([Cl:27])[CH:26]=3)([C:17]([F:19])([F:20])[F:18])[O:14][N:13]=2)=[CH:4][CH:3]=1)=[O:43]

Participants

7

Reactant 5

HCID 887MethanolHCID 6228DimethylformamideHCID 8471TriethylamineHCID 58498007HCID 58498007, compoundHCID 178418416HCID 178418416, compound

Product 1

HCID 58497930HCID 58497930, compound

Reagents, catalysts & solvents 1

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst

Procedure

To a solution of 7-bromo-4-(5-(3,5-dichlorophenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl)-2-methyl-benzo[d]oxazole (Example 6.9) (3.5 g) in dimethyl-formamide (40 ml) was added successively triethylamine (2.5 ml), methanol (60 ml) and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (“PdCl2(dppf)”) (259 mg). The reaction mixture was stirred in a pressure reactor in an atmosphere of carbon monoxide (4 bar) at 80° C. for 16 hours. The reaction mixture was cooled to ambient temperature, filtered over a plug of Celite® and concentrated. The residue was purified by column chromatography on silica gel (eluent: 15-55% v/v ethyl acetate in heptane) to give 4-(5-(3,5-dichlorophenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl)-2-methyl-benzo[d]oxazole-7-carboxylic acid methyl ester (2.75 g). 1H-NMR (400 MHz, CDCl3): 7.95-7.42 (m, 5H), 4.56 (d, 1H), 4.12 (d, 1H), 4.02 (s, 3H), 2.77 (s, 3H) ppm.

Workup

  1. filtrationfiltered over a plug of Celite®
  2. concentrationconcentrated
  3. customThe residue was purified by column chromatography on silica gel (eluent: 15-55% v/v ethyl acetate in heptane)

Sources & evidence

ORD record
ord-872bb7ab7c2847ea8abd68b91f17fbcb
Source dataset
uspto-grants-2015_12
Patent number
US09216973B2

Reaction notes

Loading…