Sodium Bicarbonate → tert-butyl (5-(4-((4S,5R)-3-(2,2-difluoroacetyl)-4-(fluoromethyl)-2,2-dimethyloxazolidin-5-yl)phenyl)pyridin-2-yl)methylcarbamate

HRID 525525Notes

Reaction equation

HRID 525525 reaction equation
[F:1][CH:2]([F:29])[C:3]([N:5]1[C@H:9]([CH2:10][F:11])[C@@H:8]([C:12]2[CH:17]=[CH:16][C:15](B3OC(C)(C)C(C)(C)O3)=[CH:14][CH:13]=2)[O:7][C:6]1([CH3:28])[CH3:27])=[O:4].Br[C:31]1[CH:32]=[CH:33][C:34]([CH2:37][NH:38][C:39](=[O:45])[O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[N:35][CH:36]=1.C(=O)(O)[O-].[Na+]>C1(C)C=CC=CC=1.C(O)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]>[F:29][CH:2]([F:1])[C:3]([N:5]1[C@H:9]([CH2:10][F:11])[C@@H:8]([C:12]2[CH:17]=[CH:16][C:15]([C:31]3[CH:32]=[CH:33][C:34]([CH2:37][NH:38][C:39](=[O:45])[O:40][C:41]([CH3:43])([CH3:42])[CH3:44])=[N:35][CH:36]=3)=[CH:14][CH:13]=2)[O:7][C:6]1([CH3:28])[CH3:27])=[O:4]

Participants

7

Reactant 3

HCID 516892Sodium BicarbonateHCID 45789881tert-Butyl ((5-bromopyridin-2-yl)methyl)carbamateHCID 866954142,2-difluoro-1-((4S,5R)-4-(fluoromethyl)-2,2-dimethyl-5-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)oxazolidin-3-yl)ethanone

Product 1

HCID 86695413tert-butyl (5-(4-((4S,5R)-3-(2,2-difluoroacetyl)-4-(fluoromethyl)-2,2-dimethyloxazolidin-5-yl)phenyl)pyridin-2-yl)methylcarbamateYield 77%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 21863594Toluene ethanolSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of the product of Step 3, Example 22 (1000 mg, 2.4 mmol) in toluene/ethanol (30:20 mL) is added commercially available tert-butyl (5-bromopyridin-2-yl)methylcarbamate (695 mg, 2.42 mmol), sodium bicarbonate (5 mL of a saturated solution) and Pd(dppf)2Cl2 (90 mg, 0.12 mmol). The reaction mixture is heated to 80° C. while stirring under nitrogen for 4 hours. The reaction mixture is cooled and diluted with water. Contents are extracted with ethylacetate (2×75 mL) and the combined organic phase is dried (Na2SO4) and concentrated under vacuum. Crude material is chromatographed (80 g Redi-Sep column) eluting from 100% hexanes to 90:10 ethylacetate:hexanes to afford the title compound (912 mg): m/z (Cl) M+H 494.

Workup

  1. temperatureThe reaction mixture is cooled
  2. extractionContents are extracted with ethylacetate (2×75 mL)
  3. dry with materialthe combined organic phase is dried (Na2SO4)
  4. concentrationconcentrated under vacuum
  5. customCrude material is chromatographed (80 g Redi-Sep column)
  6. washeluting from 100% hexanes to 90:10 ethylacetate

Sources & evidence

ORD record
ord-a25438ba19c54852b978835b938f1665
Source dataset
uspto-grants-2016_05
Patent number
US09340564B2

Reaction notes

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