Diisopropylamine → Ethyl 2-(4-chloro-6-fluoro-1-hydroxy-1-indanyl)acetate

HRID 726147Notes

Reaction equation

HRID 726147 reaction equation
[C:1]([O:4][CH2:5][CH3:6])(=[O:3])[CH3:2].C(=O)=O.CC(C)=O.C([N-]C(C)C)(C)C.[Li+].C([Li])CCC.C(NC(C)C)(C)C.[Cl:34][C:35]1[CH:43]=[C:42]([F:44])[CH:41]=[C:40]2[C:36]=1[CH2:37][CH2:38][C:39]2=[O:45].[Cl-].[NH4+]>CCCCCC.O1CCCC1.O>[Cl:34][C:35]1[CH:43]=[C:42]([F:44])[CH:41]=[C:40]2[C:36]=1[CH2:37][CH2:38][C:39]2([CH2:2][C:1]([O:4][CH2:5][CH3:6])=[O:3])[OH:45]

Participants

11

Reactant 7

HCID 7912DiisopropylamineHCID 8857Ethyl AcetateHCID 25517Ammonium ChlorideHCID 2724682Lithium diisopropylamideHCID 18522661Acetone cardice3×HCID 197103284-Chloro-6-fluoroindan-1-oneHCID 178418339Butyllithium

Product 1

HCID 10978626Ethyl 2-(4-chloro-6-fluoro-1-hydroxy-1-indanyl)acetateYield 102.2%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Procedure

Ethyl acetate (5.9 g, 0.07 mol) was added dropwise to a stirred, chilled (dry ice-acetone bath) solution of lithium diisopropylamide (prepared by dropwise addition of a 2.5M solution of n-butyllithium (26.8 ml, 0.07 mol) in hexane to a chilled (dry ice-acetone bath) solution of diisopropylamine (6.8 g, 0.07 mol) in tetrahydrofuran (35 ml) ). After 30 min, a solution of 4-chloro-6-fluoro-1-indanone (12.4 g, 0.07 mol) in tetrahydrofuran (100 ml) was added dropwise and the mixture was stirred for 1 h (dry ice-acetone bath). A solution of ammonium chloride (10.6 g, 0.20 mol) in water (80 ml) was added and the mixture was allowed to come to ambient temperature. The aqueous phase was separated and extracted with diethyl ether. The combined organic phase was dried (sodium sulphate), filtered and concentrated in vacuo to give 19.5 g of crude ethyl 2-(4-chloro-6-fluoro-1-hydroxy-1-indanyl)acetate. Chromatography on silica gel with hexanes:ethyl acetate (8:2) as eluent gave 15.2 g (83%) of a yellow oil; NMR (DMSO-d6): a 7.13-7.28 (m, 2H), 5.55 (s, 1H), 3.98 (m, 2H), 2.79 (2m's, 4H), 2.50 (m, 1H), 2.11 (m, 1H). 1.08 (t, 3H).

Workup

  1. customto come to ambient temperature
  2. customThe aqueous phase was separated
  3. extractionextracted with diethyl ether
  4. dry with materialThe combined organic phase was dried (sodium sulphate)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-cfbbfbdbceec49c9b861d6f5c98e4f5d
Source dataset
uspto-grants-1998_01
Patent number
US05708033

Reaction notes

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