Cesium carbonate → HCID 90418549, compound

HRID 2177392Notes

Reaction equation

HRID 2177392 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:12]([CH2:13][O:14][C:15]3[C:20]([F:21])=[CH:19][C:18](I)=[CH:17][C:16]=3[F:23])=[C:11]([C:24]([F:27])([F:26])[F:25])[S:10][N:9]=2)=[CH:4][CH:3]=1.C([O-])([O-])=O.[Cs+].[Cs+].C[Si](C)(C)[O:36][CH2:37][C:38]#[CH:39]>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].[Cu]I.O1CCCC1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:12]([CH2:13][O:14][C:15]3[C:20]([F:21])=[CH:19][C:18]([C:39]#[C:38][CH2:37][OH:36])=[CH:17][C:16]=3[F:23])=[C:11]([C:24]([F:27])([F:26])[F:25])[S:10][N:9]=2)=[CH:4][CH:3]=1

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 79696Silane, trimethyl(2-propyn-1-yloxy)-HCID 90418131HCID 90418131, compound

Product 1

HCID 90418549HCID 90418549, compound

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
35 °C

Procedure

Into a 50-mL 3-necked round-bottom flask (1 atm) purged and maintained with an inert atmosphere of nitrogen, was placed 3-(4-chlorophenyl)-4-(2,6-difluoro-4-iodophenoxymethyl)-5-(trifluoromethyl)-1,2-thiazole (240 mg, 0.45 mmol, 1.00 equiv), Pd(dppf)2Cl2 (15 mg, 0.02 mmol, 0.04 equiv), CuI (3.4 mg, 0.02 mmol, 0.04 equiv), Cs2CO3 (295 mg, 0.91 mmol, 2.01 equiv), trimethyl(prop-2-yn-1-yloxy)silane (116 mg, 0.90 mmol, 2.00 equiv), tetrahydrofuran (5.0 mL). The resulting solution was stirred overnight at 35° C. in an oil bath. The solvent was removed. The residue was applied onto a TLC-Plate with ethyl acetate/petroleum ether (1/6). 200 mg 3-(4-chlorophenyl)-4-((2,6-difluoro-4-(3-(trimethylsilyloxy)prop-1-ynyl)phenoxy)methyl)-5-(trifluoromethyl)isothiazole was got. Dichloromethane (3.0 mL) and TBAF (THF solution 1.0 mL) were added to the mixture. The result solution was stirred for another 3 h at 35 degree C. The resulting mixture was concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1/4). This resulted in 25 mg (12%) of 3-(4-[[3-(4-chlorophenyl)-5-(trifluoromethyl)-1,2-thiazol-4-yl]methoxy]-3,5-difluorophenyeprop-2-yn-1-ol as a light yellow solid. 1H NMR (300 MHz, CD3OD) δ 7.73 (d, J=8.4 Hz, 2H), 7.49 (d, J=8.7 Hz, 2H), 7.01 (d, J=9.0 Hz, 2H), 5.23 (s, 2H), 4.35 (s, 2H). Mass spectrum (ESI, m/z): Calcd. for C20H11ClF5NO2S, 460.0 (M+H). found 460.0.

Workup

  1. customInto a 50-mL 3-necked round-bottom flask (1 atm) purged
  2. temperaturemaintained with an inert atmosphere of nitrogen
  3. customThe solvent was removed
  4. additionDichloromethane (3.0 mL) and TBAF (THF solution 1.0 mL) were added to the mixture
  5. stirringThe result solution was stirred for another 3 h at 35 degree C
  6. concentrationThe resulting mixture was concentrated under vacuum
  7. customThis resulted in 25 mg (12%) of 3-(4-[[3-(4-chlorophenyl)-5-(trifluoromethyl)-1,2-thiazol-4-yl]methoxy]-3,5-difluorophenyeprop-2-yn-1-ol as a light yellow solid

Sources & evidence

ORD record
ord-2d8c47e154fd4f84b8f08effdfccd66e
Source dataset
uspto-grants-2015_06
Patent number
US09067898B1

Reaction notes

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