2-Fluorophenol → HCID 68543036, compound

HRID 1442961Notes

Reaction equation

HRID 1442961 reaction equation
[CH3:1][O:2][C:3]([C@@H:5]1[CH2:9][C@@H:8]([OH:10])[CH2:7][N:6]1[C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])=[O:4].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[F:37][C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][C:39]=1O.CC(OC(/N=N/C(OC(C)C)=O)=O)C>C1COCC1>[CH3:1][O:2][C:3]([CH:5]1[CH2:9][CH:8]([O:10][C:39]2[CH:40]=[CH:41][CH:42]=[CH:43][C:38]=2[F:37])[CH2:7][N:6]1[C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])=[O:4]

Participants

6

Reactant 4

HCID 97072-FluorophenolHCID 11776TriphenylphosphineHCID 2734883(2S,4R)-4-Hydroxypyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl esterHCID 5363146Diisopropyl azodicarboxylate

Product 1

HCID 68543036HCID 68543036, compoundYield 58%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

(2S,4R)-4-Hydroxy-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester (CAS Reg. No. 74844-91-0) (300 mg, 1.22 mmol) was dissolved in THF (10 ml), and triphenylphosphine (385 mg, 1.47 mmol) and 2-fluorophenol (164.5 mg, 1.47 mmol) were added. The reaction was cooled in ice, DIAD (0.23 ml, 1.2 mmol) added dropwise and the reaction stirred at room temperature overnight. The mixture was concentrated in vacuo, CH2Cl2 (20 ml) added and the solution washed with 2N NaOH (10 ml). The phases were separated and the organic phase washed with saturated brine (10 ml), dried over MgSO4 and evaporated. The residue was dissolved in a minimum of diethylether and pentane added until solution just maintained. After seeding with triphenylphosphine oxide, the solution was cooled in ice and the resultant precipitate filtered. The filtrate was evaporated and the residue purified by flash chromatography on silica (50 g) eluting initially with pentane:diethylether (2:1 by volume), then pentane:diethylether (1:1 by volume) to give the title product (388 mg, 58%) as an impure oil containing diisopropylbicarbamate as an impurity.

Workup

  1. temperatureThe reaction was cooled in ice
  2. concentrationThe mixture was concentrated in vacuo, CH2Cl2 (20 ml)
  3. additionadded
  4. washthe solution washed with 2N NaOH (10 ml)
  5. customThe phases were separated
  6. washthe organic phase washed with saturated brine (10 ml)
  7. dry with materialdried over MgSO4
  8. customevaporated
  9. dissolutionThe residue was dissolved in a minimum of diethylether and pentane
  10. additionadded until solution
  11. temperaturejust maintained
  12. temperaturethe solution was cooled in ice
  13. filtrationthe resultant precipitate filtered
  14. customThe filtrate was evaporated
  15. customthe residue purified by flash chromatography on silica (50 g)
  16. washeluting initially with pentane:diethylether (2:1 by volume)

Sources & evidence

ORD record
ord-d2b4f6f61b7c44ccbc215327312c6d9a
Source dataset
uspto-grants-2010_02
Patent number
US07659305B2

Reaction notes

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