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

HRID 1027405Notes

Reaction equation

HRID 1027405 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C:12]1[CH:17]=[CH:16][C:15](B(O)O)=[CH:14][CH:13]=1)=[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:29]([Si:33]([CH3:50])([CH3:49])[O:34][CH:35]1[CH2:40][CH2:39][C:38](OS(C(F)(F)F)(=O)=O)=[CH:37][CH2:36]1)([CH3:32])([CH3:31])[CH3:30]>C1(C)C=CC=CC=1.CCOC(C)=O.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:38]2[CH2:39][CH2:40][CH:35]([O:34][Si:33]([C:29]([CH3:32])([CH3:31])[CH3:30])([CH3:49])[CH3:50])[CH2:36][CH:37]=2)=[CH:14][CH:13]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

10

Reactant 4

HCID 10340Sodium CarbonateHCID 433294Lithium ChlorideHCID 27733224-(Benzyloxycarbonylamino)phenylboronic Acid (contains varying amounts of Anhydride)HCID 534150124-((tert-Butyldimethylsilyl)oxy)cyclohex-1-en-1-yl trifluoromethanesulfonate

Product 1

HCID 67478826{4-[4-(tert-Butyl-dimethyl-silanyloxy)-cyclohex-1-enyl]-phenyl}-carbamic acid benzyl esterYield 98%

Reagents, catalysts & solvents 5

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

4-Benzyloxycarbonylamino-benzene boronic acid (1.42 g, 5.25 mmol, 1.5 equiv.) and LiCl (420 mg, 10.5 mmol, 3 equiv.) was placed in a 25 mL round bottom flask. To this was added Na2CO3 (2M) (7 mL) and EtOH (7 mL) to form a nice suspension. To this was transferred a solution of trifluoromethanesulfonic acid 4-(tert-butyl-dimethyl-silanyloxy)-cyclohex-1-enyl ester (1.26 g, 3.5 mmol, 1 equiv.) in toluene (18 mL). This suspension was subjected to a vacuum/nitrogen exchange three times. Pd(PPh3)4 (CAS 14221-01-3) (203 mg, 0.05 mmol, 7.5 mol %) was then added. The brown mixture was heated in an oil bath at 100° C. (external) for 50 min when the suspension became dark. At which time the TLC showed that the reaction was complete. The reaction was diluted with EtOAc (20 mL) and water (10 mL). The two layers were separated, and the aqueous layer was extracted with EtOAc (10 mL×2). The combined EtOAc extracts were washed with sodium bicarbonate (5 mL), brine (5 mL), dried (anhydrous potassium carbonate), filtered, and concentrated in vacuo to obtain a crude product. This was purified on a silica gel column eluted with 30% EtOAc in heptane to afford 1.5 g (98% yield) of the title compound as a crystalline white solid.

Workup

  1. customto form a nice suspension
  2. customThe two layers were separated
  3. extractionthe aqueous layer was extracted with EtOAc (10 mL×2)
  4. washThe combined EtOAc extracts were washed with sodium bicarbonate (5 mL), brine (5 mL)
  5. dry with materialdried (anhydrous potassium carbonate)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto obtain a crude product
  9. customThis was purified on a silica gel column
  10. washeluted with 30% EtOAc in heptane

Sources & evidence

ORD record
ord-36ff28766c3c4b42b72d2b8017d3a161
Source dataset
uspto-grants-2014_05
Patent number
US08735385B2

Reaction notes

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