Hydrochloric Acid → HCID 23293613, compound

HRID 1954891Notes

Reaction equation

HRID 1954891 reaction equation
C(=O)=O.CC(C)=O.C(NC(C)C)(C)C.C([Li])CCC.Cl[Si](C)(C)C.[F:25][C:26]1[CH:35]=[C:34]2[C:29]([CH2:30][CH2:31][CH2:32][CH:33]2[CH2:36][C:37]([O:39][CH2:40][CH3:41])=[O:38])=[CH:28][CH:27]=1.[Br:42]N1C(=O)CCC1=O.Cl>O1CCCC1.CCCCCC>[Br:42][CH:36]([CH:33]1[C:34]2[C:29](=[CH:28][CH:27]=[C:26]([F:25])[CH:35]=2)[CH2:30][CH2:31][CH2:32]1)[C:37]([O:39][CH2:40][CH3:41])=[O:38]

Participants

10

Reactant 7

HCID 313Hydrochloric AcidHCID 6397ChlorotrimethylsilaneHCID 7912DiisopropylamineHCID 67184N-bromobutanimideHCID 18522661Acetone cardice2×HCID 23293573HCID 23293573, compoundHCID 178418339Butyllithium

Product 1

HCID 23293613HCID 23293613, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent

Procedure

To a stirred, chilled (dry ice-acetone bath) solution of diisopropylamine (0.3 mL, 1.9 mmol, Aldrich) in tetrahydrofuran (3 mL) under nitrogen was successively added 2.5N n-butyl lithium in hexane (0.8 mL, Aldrich), chlorotrimethylsilane (0.2 mL, 1.8 mmol, Aldrich) and ethyl 2-(7-fluoro-1,2,3,4-tetrahydro-1-naphthyl)acetate (236 mg, 1.0 mmol). The resulting clear solution was stirred for 1 h, treated with N-bromosuccinimide (180 mg, 1.0 mmol, Aldrich) and stirred for an additional 0.5 h before the dry ice-acetone bath was removed. The reddish cloudy solution was stirred for 2 h at room temperature, treated with dilute aq hydrochloric acid (4 meq) and extracted with diethyl ether (30 mL). The ether layer was dried over anhydrous sodium sulfate, filtered, concentrated in vacuo and chromatographed on Silica Gel 60 using dichloromethane-hexane (1:9) as eluent. Fractions containing only ethyl 2-bromo-2-(7-fluoro-1,2,3,4-tetrahydro-1-naphthyl)acetate as a 1:4 isomeric mixture were combined and concentrated in vacuo to a clear oil (171 mg, 54%); NMR (DMSO-d6): d 7.00-7.18 (m, 3H, Ar), 5.20 (d, J=6.2 Hz, 0.8H, BrCHCO), 5.17 (d, J=6.2 Hz, 0.2H, BrCHCO), 4.19 (q, 1.6H, CH2OOC), 4.14 (q, 0.4H, CH2OOC), 3.49 (m, 1H, ArCH), 2.69 (m, 2H, ArCH2), 1.81-1.97 (m, 3H, CH, CH2), 1.61-1.67 (m, 1H, CH), 1.21 (t, 2.4H, CH3), 1.07 (t, 0.6H, CH3).

Workup

  1. customwas removed
  2. stirringThe reddish cloudy solution was stirred for 2 h at room temperature
  3. extractionextracted with diethyl ether (30 mL)
  4. dry with materialThe ether layer was dried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customchromatographed on Silica Gel 60 using dichloromethane-hexane (1:9) as eluent
  8. additionFractions containing only ethyl 2-bromo-2-(7-fluoro-1,2,3,4-tetrahydro-1-naphthyl)acetate as a 1:4 isomeric mixture
  9. concentrationconcentrated in vacuo to a clear oil (171 mg, 54%)

Sources & evidence

ORD record
ord-ffb235ef33044f2ab493e4a22e0fc3e9
Source dataset
uspto-grants-2000_09
Patent number
US06124284

Reaction notes

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