2-Chloroethyl chloroformate → 6-chloro-3H-spiro[isobenzofuran-1,4'-piperidine]

HRID 270050Notes

Reaction equation

HRID 270050 reaction equation
C([N:8]1[CH2:13][CH2:12][C:11]2([C:17]3[CH:18]=[C:19]([Cl:22])[CH:20]=[CH:21][C:16]=3[CH2:15][O:14]2)[CH2:10][CH2:9]1)C1C=CC=CC=1.ClC(OCCCl)=O>ClCCl>[Cl:22][C:19]1[CH:20]=[CH:21][C:16]2[CH2:15][O:14][C:11]3([CH2:10][CH2:9][NH:8][CH2:13][CH2:12]3)[C:17]=2[CH:18]=1

Participants

4

Reactant 2

HCID 123052-Chloroethyl chloroformateHCID 598336401'-Benzyl-6-chloro-3H-spiro[isobenzofuran-1,4'-piperidine]

Product 1

HCID 468354386-chloro-3H-spiro[isobenzofuran-1,4'-piperidine]Yield 28.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 1′-benzyl-6-chloro-3H-spiro[2-benzofuran-1,4′-piperidine] (850 mg, 2.7 mmol) in dichloromethane (CH2Cl2) (8 mL) was added chloroethyl chloroformate (Yang, B. V; o'Rourke, D; Li, J., Synlett, 1993, 195-196) (772 mg, 5.4 mmol) slowly at 0° C. After addition was complete the reaction mixture was stirred at 0° C. for 30 min. The volatiles were removed in vacuo, residue was dissolved in methanol (10 mL) and kept at reflux for 40 min. The volatiles were removed in vacuo and the residue was purified by silica gel flash chromatography (0-6% methanol in dichloromethane, 0.2% ammonium hydroxide (NH4OH)) to give the titled compound (170 mg) and 1′-benzyl-6-chloro-3H-spiro[2-benzofuran-1,4′-piperidine] was recovered (200 mg).

Workup

  1. additionAfter addition
  2. customThe volatiles were removed in vacuo, residue
  3. dissolutionwas dissolved in methanol (10 mL)
  4. temperatureat reflux for 40 min
  5. customThe volatiles were removed in vacuo
  6. customthe residue was purified by silica gel flash chromatography (0-6% methanol in dichloromethane, 0.2% ammonium hydroxide (NH4OH))

Sources & evidence

ORD record
ord-51fb170678724e6b9680f23f8f15607d
Source dataset
uspto-grants-2008_11
Patent number
US07449475B2

Reaction notes

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