Hydrochloric Acid → Ethyl 2-(6-fluoro-1-hydroxy-1-indanyl)acetate

HRID 862756Notes

Reaction equation

HRID 862756 reaction equation
[C:1]([O:4][CH2:5][CH3:6])(=[O:3])[CH3:2].C(=O)=O.CC(C)=O.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[F:24][C:25]1[CH:33]=[C:32]2[C:28]([CH2:29][CH2:30][C:31]2=[O:34])=[CH:27][CH:26]=1.Cl>O1CCCC1>[F:24][C:25]1[CH:33]=[C:32]2[C:28]([CH2:29][CH2:30][C:31]2([CH2:2][C:1]([O:4][CH2:5][CH3:6])=[O:3])[OH:34])=[CH:27][CH:26]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 8857Ethyl AcetateHCID 15194646-Fluoro-1-indanoneHCID 2733832Lithium HexamethyldisilazideHCID 18522661Acetone cardice

Product 1

HCID 23293626Ethyl 2-(6-fluoro-1-hydroxy-1-indanyl)acetateYield 65.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Ethyl acetate (1.8 g, 20 mmol) was added dropwise to a stirred, chilled (dry ice-acetone bath) 1N solution of lithium bis(trimethylsilyl)amide in tetrahydrofuran (20 mL, Aldrich) under nitrogen. After 15 min, a solution of 6-fluoro-1-indanone (3.0 g, 20 mmol) in tetrahyrofuran (20 mL) was added dropwise and the resulting mixture was stirred for 1h (dry ice-acetone bath). A 1N solution of hydrochloric acid (20 mL) was added and the mixture was allowed to warm to more temperature. The organic phase was separated, dried over anhydrous sodium sulfate, filtered and concentrated to a pale yellow oil (5.3 g). The mixture was chromatographed on Silica Gel 60 (silica gel) using a linear gradient of dichloromethane- hexanes (1:1) to dichloromethane as eluent. The fractions containing only ethyl 2-(6-fluoro-1-hydroxy-1-indanyl)acetate were combined and concentrated in vacuo to give 3.1 g (65%) of a colorless oil; NMR (DMSO-d6): d 6.98-7.27 (m, 3H, Ar), 5.40 (s, 1H, OH), 4.01 (q, 2H, OCH2), 2.64-2.96 (m, 4H, 2XCH2), 2.44-2.57 (m, 1H, CH), 2.04-2.18 (m, 1H, CH), 1.12 (t, 3H, CH3).

Workup

  1. temperatureto warm to more temperature
  2. customThe organic phase was separated
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated to a pale yellow oil (5.3 g)
  6. customThe mixture was chromatographed on Silica Gel 60 (silica gel)
  7. additionThe fractions containing only ethyl 2-(6-fluoro-1-hydroxy-1-indanyl)acetate
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-470a3ad4d51f4569887408fff93388fa
Source dataset
uspto-grants-1998_02
Patent number
US05719186

Reaction notes

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