Sodium Carbonate → {4-[4-(tert-Butyl-dimethyl-silanyloxy)-cyclohex-1-enyl]-2-fluoro-phenyl}-carbamic acid benzyl ester

HRID 1027409Notes

Reaction equation

HRID 1027409 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C:12]1[CH:17]=[CH:16][C:15](B(O)O)=[CH:14][C:13]=1[F:21])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Li+].[Cl-].C([O-])([O-])=O.[Na+].[Na+].[C:30]([Si:34]([CH3:51])([CH3:50])[O:35][CH:36]1[CH2:41][CH2:40][C:39](OS(C(F)(F)F)(=O)=O)=[CH:38][CH2:37]1)([CH3:33])([CH3:32])[CH3:31]>C1(C)C=CC=CC=1.CCOCC.O.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.CCO>[CH2:1]([O:8][C:9](=[O:10])[NH:11][C:12]1[CH:17]=[CH:16][C:15]([C:39]2[CH2:40][CH2:41][CH:36]([O:35][Si:34]([C:30]([CH3:33])([CH3:32])[CH3:31])([CH3:50])[CH3:51])[CH2:37][CH:38]=2)=[CH:14][C:13]=1[F:21])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

10

Reactant 4

HCID 10340Sodium CarbonateHCID 433294Lithium ChlorideHCID 44717603(4-(((Benzyloxy)carbonyl)amino)-3-fluorophenyl)boronic acidHCID 534150124-((tert-Butyldimethylsilyl)oxy)cyclohex-1-en-1-yl trifluoromethanesulfonate

Product 1

HCID 67479117{4-[4-(tert-Butyl-dimethyl-silanyloxy)-cyclohex-1-enyl]-2-fluoro-phenyl}-carbamic acid benzyl esterYield 77%

Reagents, catalysts & solvents 5

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 1140TolueneSolventHCID 3283Diethyl EtherSolvent

Conditions

Temperature
100 °C

Procedure

4-Benzyloxycarbonylamino-3-fluoro-benzene boronic acid (2.53 g, 8.75 mmol, 1.25 equiv.) and LiCl (840 mg, 21 mmol, 3.0 equiv.) was placed in a 125 mL round bottom flask equipped with a condenser. To this was added aq. Na2CO3 (2 M, 14 mL) and EtOH (14 mL) to form a nice suspension. To this was transferred a solution of trifluoromethanesulfonic acid 4-(tert-butyl-dimethyl-silanyloxy)-cyclohex-1-enyl ester (2.52 g, 7 mmol, 1 equiv.) in toluene (36 mL). This suspension was subjected to a vacuum/nitrogen exchange three times. Pd(PPh3)4 (CAS 14221-01-3) (406 mg, 0.10 mmol, 7.5 mol %) was then added. The brown mixture was heated in an oil bath at 100° C. for 40 min when the suspension became dark. TLC showed the reaction was complete. The reaction was diluted with ether (20 mL) and water (20 mL). The two layers were separated, and the aqueous layer was extracted with Et2O (2×10 mL). The combined Et2O extracts were washed with sodium bicarbonate (5 mL), brine (5 mL) and dried (anhydrous potassium carbonate). The solution was passed through a short Celite/silica gel pad, eluted with EtOAc. The filtrate was concentrated in vacuo to obtain a crude product. This was purified on silica gel column to get a solid. The solid was crystallized in 10% EtOAc in heptane to get 2.45 g (77%) of the title compound as a white crystalline solid. mp 116.1-119° C.

Workup

  1. customequipped with a condenser
  2. customto form a nice suspension
  3. customThe two layers were separated
  4. extractionthe aqueous layer was extracted with Et2O (2×10 mL)
  5. washThe combined Et2O extracts were washed with sodium bicarbonate (5 mL), brine (5 mL)
  6. dry with materialdried (anhydrous potassium carbonate)
  7. washeluted with EtOAc
  8. concentrationThe filtrate was concentrated in vacuo
  9. customto obtain a crude product
  10. customThis was purified on silica gel column
  11. customto get a solid
  12. customThe solid was crystallized in 10% EtOAc in heptane

Sources & evidence

ORD record
ord-cfe131a8e6c0434faca27732b1a00631
Source dataset
uspto-grants-2014_05
Patent number
US08735385B2

Reaction notes

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