Sodium Carbonate → HCID 71571902, compound

HRID 1750813Notes

Reaction equation

HRID 1750813 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4](B2OC(C)(C)C(C)(C)O2)[CH:5]=[C:6]([F:9])[C:7]=1[F:8].Br[C:20]([C:22]([F:25])([F:24])[F:23])=[CH2:21].C([O-])([O-])=O.[Na+].[Na+].[OH:32][N:33]=[C:34](Cl)[C:35]1[CH:46]=[CH:45][C:38]2[B:39]([OH:44])[O:40][C:41]([CH3:43])([CH3:42])[C:37]=2[CH:36]=1>COCCOC.O.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]>[Cl:1][C:2]1[CH:3]=[C:4]([C:20]2([C:22]([F:25])([F:24])[F:23])[O:32][N:33]=[C:34]([C:35]3[CH:46]=[CH:45][C:38]4[B:39]([OH:44])[O:40][C:41]([CH3:43])([CH3:42])[C:37]=4[CH:36]=3)[CH2:21]2)[CH:5]=[C:6]([F:9])[C:7]=1[F:8]

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 2726961-Propene, 2-bromo-3,3,3-trifluoro-HCID 86685046N,1-dihydroxy-3,3-dimethyl-1,3-dihydrobenzo[c][1,2]oxaborole-5-carbimidoyl chlorideHCID 86685066HCID 86685066, compound

Product 1

HCID 71571902HCID 71571902, compoundYield 8%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
75 °C

Procedure

A mixture of 2-(3-chloro-4,5-difluorophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1.2 g, 4.38 mmol), 2-bromo-3,3,3-trifluoroprop-1-ene (920 mg, 5.26 mmol, 1.2 eq), Na2CO3 (1.39 g, 13.14 mmol, 3 eq) and Pd(dppf)Cl2 (358 mg, 10% mol) in DME (50 mL) and water (2 mL) was heated at 70 to 80° C. for 2 h. The mixture was cooled to 0° C. with ice-water bath, and then used to next step without work-up. To the reaction mixture were added TEA (1.33 g, 1.83 mL, 13.14 mmol, 3 eq) and N,1-dihydroxy-3,3-dimethyl-1,3-dihydrobenzo[c][1,2]oxaborole-5-carbimidoyl chloride (841 mg, 3.50 mmol, 0.8 eq) at 0° C. The reaction mixture was stirred for 12 h at rt, poured into ice-water and extracted with EA. The organic layer was washed with brine, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by silica gel column and prep-HPLC to give 125 mg final title product. 1H NMR (400 MHz, DMSO-d6): δ 9.22 (s, 1 H), 7.76-7.66 (m, 5 H), 4.43 (d, J=18.4 Hz, 1 H), 4.31 (d, J=18.4 Hz, 1 H), 1.48 (s,6 H) ppm; MS: m/z=444/504 (M−1, ESI−).

Workup

  1. temperatureThe mixture was cooled to 0° C. with ice-water bath
  2. extractionextracted with EA
  3. washThe organic layer was washed with brine
  4. dry with materialdried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel column

Sources & evidence

ORD record
ord-dba14642ab904512b1ff7b13e62e8968
Source dataset
uspto-grants-2015_10
Patent number
US09156860B2

Reaction notes

Loading…