Benzyl chloroformate → (+/-)-1-(5-Fluoro-2-hydroxy-phenyl)-1,3-dihydro-isoindole-2-carboxylic acid benzyl ester

HRID 2036240Notes

Reaction equation

HRID 2036240 reaction equation
[CH:1]1([C:10]2[CH:15]=[C:14]([F:16])[CH:13]=[CH:12][C:11]=2[OH:17])[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][NH:2]1.CCN(C(C)C)C(C)C.Cl[C:28]([O:30][CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)=[O:29]>C(Cl)Cl>[CH2:31]([O:30][C:28]([N:2]1[CH2:3][C:4]2[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=2)[CH:1]1[C:10]1[CH:15]=[C:14]([F:16])[CH:13]=[CH:12][C:11]=1[OH:17])=[O:29])[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1

Participants

5

Reactant 3

HCID 10387Benzyl chloroformateHCID 81531DiisopropylethylamineHCID 66654979(+/-)-2-(2,3-dihydro-1H-isoindol-1-yl)-4-fluoro-phenol

Product 1

HCID 66653980(+/-)-1-(5-Fluoro-2-hydroxy-phenyl)-1,3-dihydro-isoindole-2-carboxylic acid benzyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To an-ice cooled solution of (±)-2-(2,3-dihydro-1H-isoindol-1-yl)-4-fluoro-phenol (13 mg, 0.055 mmol, 1.00 eq.) and DIPEA (37 μL, 0.218 mmol, 4.00 eq.) in DCM (2 mL), benzyl chloroformate (8 μL, 0.057 mmol, 1.05 eq.) was added dropwise. Upon completion of the addition, the cooling bath was removed and the solution was stirred at r.t. for 3 hours. The reaction was quenched with 1M aq. citric acid soln. (5 mL). The layers were separated. The aq. phase was extracted with DCM (3×2 mL). The comb. org. phases were dried over MgSO4 and concentrated in vacuo. The residue was purified by prep. HPLC (column: Atlantis, 30×75 mm, 10 um, UV/MS, acidic conditions) and concentrated in vacuo to give (±)-1-(5-fluoro-2-hydroxy-phenyl)-1,3-dihydro-isoindole-2-carboxylic acid benzyl ester.

Workup

  1. additionUpon completion of the addition
  2. customthe cooling bath was removed
  3. customThe reaction was quenched with 1M aq. citric acid soln
  4. customThe layers were separated
  5. extractionThe aq. phase was extracted with DCM (3×2 mL)
  6. dry with materialphases were dried over MgSO4
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by prep
  9. concentrationHPLC (column: Atlantis, 30×75 mm, 10 um, UV/MS, acidic conditions) and concentrated in vacuo

Sources & evidence

ORD record
ord-e174543013f6451f9689b6dc7de58388
Source dataset
uspto-grants-2013_11
Patent number
US08575158B2

Reaction notes

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