Water → HCID 18665556, compound

HRID 2395387Notes

Reaction equation

HRID 2395387 reaction equation
[Si:1]([O:8][C:9]1[C:10]([F:18])=[C:11]([CH:15]=[CH:16][CH:17]=1)[C:12]([OH:14])=O)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].S(Cl)(Cl)=O.C([N:25]([CH2:28][CH3:29])CC)C.[OH2:30]>C1(C)C=CC=CC=1.C(Cl)Cl>[Si:1]([O:8][C:9]1[C:10]([F:18])=[C:11]([CH:15]=[CH:16][CH:17]=1)[C:12]([NH:25][CH2:28][C@H:29]([C:9]1[CH:10]=[CH:11][CH:15]=[CH:16][CH:17]=1)[OH:30])=[O:14])([C:4]([CH3:5])([CH3:6])[CH3:7])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 24386Thionyl ChlorideHCID 18971692HCID 18971692, compound

Product 1

HCID 18665556HCID 18665556, compoundYield 97%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 3-tert-butyldimethylsilyloxy-2-fluorobenzoic acid (3.3 g, 12 mmol, example 36B) in toluene (30 ml) was added thionyl chloride (1.3 ml, 18 mmol) carefully at ambient temperature. After addition was complete, the reaction mixture was heated at reflux for 40 min, then cooled and concentrated in vacuo. The residual oil was dissolved in CH2Cl2 (20 ml) and added dropwise to a solution of (+)-2-amino-1(S)-phenylethanol (1.7 g, 12 mmol, see A. I. Meyers and J. Slade. J. Org. Chem. 1980, 45, 2785.) and triethylamine (2.0 ml, 15 mmol) in CH2Cl2 (20 ml) cooled to 0° C. The reaction mixture was allowed to warm to ambient temperature and stirred a further 30 min. The mixture was poured into water (100 ml) and extracted with CH2 Cl2 (3×10 ml). The combined organic extracts were washed with saturated aqueous NaHCO3 (100 ml), dried (MgSO4) and concentrated under reduced pressure. The crude product was purified by column chromatography on silica gel eluting with hexane/ethyl acetate (=3:2) to afford title compound (4.6 g, 97%) as a pale yellow liquid.

Workup

  1. additionAfter addition
  2. temperaturethe reaction mixture was heated
  3. temperatureat reflux for 40 min
  4. temperaturecooled
  5. concentrationconcentrated in vacuo
  6. dissolutionThe residual oil was dissolved in CH2Cl2 (20 ml)
  7. additionadded dropwise to a solution of (+)-2-amino-1(S)-phenylethanol (1.7 g, 12 mmol
  8. extractionextracted with CH2 Cl2 (3×10 ml)
  9. washThe combined organic extracts were washed with saturated aqueous NaHCO3 (100 ml)
  10. dry with materialdried (MgSO4)
  11. concentrationconcentrated under reduced pressure
  12. customThe crude product was purified by column chromatography on silica gel eluting with hexane/ethyl acetate (=3:2)

Sources & evidence

ORD record
ord-828c6e99f193464fbcd5ee3405dc59d1
Source dataset
uspto-grants-1998_09
Patent number
US05814648

Reaction notes

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