Triethylamine → Methanesulfonic acid 4-(4-benzyloxycarbonylamino-3-fluoro-phenyl)-cyclohex-3-enyl ester

HRID 1027411Notes

Reaction equation

HRID 1027411 reaction equation
[CH2:1]([O:8][C:9](=[O:25])[NH:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]2[CH2:22][CH2:21][CH:20]([OH:23])[CH2:19][CH:18]=2)=[CH:13][C:12]=1[F:24])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CCN(CC)CC.[CH3:33][S:34](Cl)(=[O:36])=[O:35].CCOC(C)=O>C(Cl)Cl.CCCCCCC>[CH2:1]([O:8][C:9]([NH:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]2[CH2:22][CH2:21][CH:20]([O:23][S:34]([CH3:33])(=[O:36])=[O:35])[CH2:19][CH:18]=2)=[CH:13][C:12]=1[F:24])=[O:25])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 8857Ethyl AcetateHCID 31297Methanesulfonyl chlorideHCID 67479441[2-Fluoro-4-(4-hydroxy-cyclohex-1-enyl)-phenyl]-carbamic acid benzyl ester

Product 1

HCID 86678095Methanesulfonic acid 4-(4-benzyloxycarbonylamino-3-fluoro-phenyl)-cyclohex-3-enyl esterYield 88.2%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8900HeptaneSolvent

Procedure

To a solution of [2-fluoro-4-(4-hydroxy-cyclohex-1-enyl)-phenyl]-carbamic acid benzyl ester (230 mg. 0.67 mmol) in DCM (5 mL) was added Et3N (0.2 mL, 1.7 mmol, 2 equiv.). The solution was cooled to an ice-water bath and then de-aerated by vacuum/nitrogen exchange. To this solution was transferred a solution of methanesulfonyl chloride (146 mg, 1.2 mmol, 1.5 equiv.) in DCM (2 mL). The clear solution was stirred in an ice-water bath for 1 h. TLC (50% EtOAc in heptane) indicated that the reaction was complete. The reaction was quenched by diluting with DCM (10 mL), followed by addition of NaHCO3 aq. (5 mL). The two layers were separated and the aqueous layer was extracted with DCM (2×5 mL). The combined extracts were washed with NaHCO3 aq. (5 mL), brine (5 mL), and dried (K2CO3). The solution was filtered through a silica gel pad, eluted with 5% MeOH in DCM to afford 248 mg (88%) of the title compound.

Workup

  1. temperatureThe solution was cooled to an ice-water bath
  2. customThe reaction was quenched
  3. additionby diluting with DCM (10 mL)
  4. additionfollowed by addition of NaHCO3 aq. (5 mL)
  5. customThe two layers were separated
  6. extractionthe aqueous layer was extracted with DCM (2×5 mL)
  7. washThe combined extracts were washed with NaHCO3 aq. (5 mL), brine (5 mL)
  8. dry with materialdried (K2CO3)
  9. filtrationThe solution was filtered through a silica gel pad
  10. washeluted with 5% MeOH in DCM

Sources & evidence

ORD record
ord-6c50521d01d246728fa19b6c24099209
Source dataset
uspto-grants-2014_05
Patent number
US08735385B2

Reaction notes

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