Dichloromethane → (S)-ethyl 2-(tert-butoxy)-2-(2-(2-chloro-5-methylpyridin-4-yl)-7-(4-chlorophenyl)-5-methylbenzo[d]thiazol-6-yl)acetate

HRID 879524Notes

Reaction equation

HRID 879524 reaction equation
Br[C:2]1[C:7]([CH3:8])=[CH:6][N:5]=[C:4]([Cl:9])[CH:3]=1.B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.C(Cl)Cl.CC([O-])=O.[K+].Br[C:37]1[S:38][C:39]2[C:45]([C:46]3[CH:51]=[CH:50][C:49]([Cl:52])=[CH:48][CH:47]=3)=[C:44]([C@H:53]([O:59][C:60]([CH3:63])([CH3:62])[CH3:61])[C:54]([O:56][CH2:57][CH3:58])=[O:55])[C:43]([CH3:64])=[CH:42][C:40]=2[N:41]=1.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.CCOC(C)=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].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:60]([O:59][C@@H:53]([C:44]1[C:43]([CH3:64])=[CH:42][C:40]2[N:41]=[C:37]([C:2]3[C:7]([CH3:8])=[CH:6][N:5]=[C:4]([Cl:9])[CH:3]=3)[S:38][C:39]=2[C:45]=1[C:46]1[CH:47]=[CH:48][C:49]([Cl:52])=[CH:50][CH:51]=1)[C:54]([O:56][CH2:57][CH3:58])=[O:55])([CH3:61])([CH3:62])[CH3:63]

Participants

11

Reactant 6

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 534399184-Bromo-2-chloro-5-methylpyridineHCID 86700141(S)-ethyl 2-(2-bromo-7-(4-chlorophenyl)-5-methylbenzo[d]thiazol-6-yl)-2-tert-butoxyacetate

Product 1

HCID 86700344(S)-ethyl 2-(tert-butoxy)-2-(2-(2-chloro-5-methylpyridin-4-yl)-7-(4-chlorophenyl)-5-methylbenzo[d]thiazol-6-yl)acetate

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A microwave vial was charged with 4-bromo-2-chloro-5-methylpyridine (199 mg, 0.96 mmol), Bis(pinacolato)diboron (252 mg, 0.99 mmol), PdCl2(dppf).CH2Cl2 (44 mg, 0.05 mmol), then KOAc (293 mg, 2.98 mmol). The vial was flushed with argon, diluted with dioxane (4 mL), sealed, then heated to 100° C. for 1 hour. The reaction mixture was allowed to cool to room temperature and then a portion of this cooled solution (0.7 mL, 0.17 mmol) was added to a vial that was charged with (S)-ethyl 2-(2-bromo-7-(4-chlorophenyl)-5-methylbenzo[d]thiazol-6-yl)-2-tert-butoxyacetate (80 mg, 0.16 mmol) and Pd(PPh3)4 (9 mg, 0.01 mmol). The mixture was diluted with dioxane (2.0 mL) and to this was added 2M aqueous K2CO3 (0.30 mL, 0.60 mmol). The vial was sealed, heated to 100° C. for 1 hour, and then allowed to cool to room temperature. The mixture was diluted with EtOAc, dried over Na2SO4, filtered, and concentrated in vacuo. The crude residue was purified by silica gel column chromatography (0-20% EtOAc/Hex gradient) to afford the desired product. LCMS-ESL': calc'd C28H29Cl2N2O3S: 543.1 (M+H+); Found: 543.2 (M+H+).

Workup

  1. customThe vial was flushed with argon
  2. additiondiluted with dioxane (4 mL)
  3. customsealed
  4. temperatureto cool to room temperature
  5. customThe vial was sealed
  6. temperatureheated to 100° C. for 1 hour
  7. temperatureto cool to room temperature
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe crude residue was purified by silica gel column chromatography (0-20% EtOAc/Hex gradient)

Sources & evidence

ORD record
ord-e1dd60025faf46cea8e0965f3e9d4f34
Source dataset
uspto-grants-2015_03
Patent number
US08987250B2

Reaction notes

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