1-Chloroethyl chloroformate → HCID 69292171, compound

HRID 899098Notes

Reaction equation

HRID 899098 reaction equation
C([N:8]1[CH2:13][CH2:12][O:11][CH:10]([C:14]([C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([F:30])[CH:25]=2)([OH:23])[CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[Cl:22])[CH2:9]1)C1C=CC=CC=1.CC(Cl)OC(Cl)=O>ClCCCl>[ClH:22].[Cl:22][C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=1[CH2:15][C@:14]([C:24]1[CH:29]=[CH:28][CH:27]=[C:26]([F:30])[CH:25]=1)([C@@H:10]1[O:11][CH2:12][CH2:13][NH:8][CH2:9]1)[OH:23]

Participants

4

Reactant 2

HCID 5213051-Chloroethyl chloroformateHCID 69289136HCID 69289136, compound

Product 1

HCID 69292171HCID 69292171, compoundYield 18%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To a solution of 1-(4-Benzyl-morpholine-2-yl)-2-(2-chloro-phenyl)-1-(3-fluoro-phenyl)-ethanol. (3.2 g, 1 equiv.) in dry 1,2-dichloroethane (40 mL) under nitrogen atmosphere was added ACE-Cl (20.33 g, 5 equiv.). The reaction mixture was stirred at room temperature overnight then refluxed until completion. All volatiles were evaporated under vacuum, and the resulting residue redissolved in acetonitrile. This solution was filtered through an ion exchange column and the filtrate taken-up with methanol (50 mL) and refluxed for 3 h. The solution was again filtered through acid ion exchange column and the required fractions evaporated to dryness. The resulting solid was next purified via preparative HPLC followed by chiral HPLC. The purified active enantiomer was taken up in ethanol and hydrogen chloride was added (large excess of 2M solution in diethyl ether) and the mixture stirred. Then all the volatiles were evaporated in vacuo, to give 519 mg of the title compound as a white solid (18%). 1H NMR (300 MHz, DMSO D6) δ: 2.43-2.54 (m, 1H), 2.81-2.95 (m, 2H), 3.16-3.23 (m, 1H), 3.30-3.44 (m, 2H), 3.54 (bs, 1H), 3.92-4.00 (m, 1H), 4.15-4.23 (m, 2H), 6.96-7.29 (m, 8H), 9.32-9.45 (m, 2H). LCMS (12 minute method) [M+H]+=336.

Workup

  1. temperaturethen refluxed until completion
  2. customAll volatiles were evaporated under vacuum
  3. dissolutionthe resulting residue redissolved in acetonitrile
  4. filtrationThis solution was filtered through an ion exchange column
  5. temperaturethe filtrate taken-up with methanol (50 mL) and refluxed for 3 h
  6. filtrationThe solution was again filtered through acid ion exchange column
  7. customthe required fractions evaporated to dryness
  8. customThe resulting solid was next purified via preparative HPLC
  9. additionhydrogen chloride was added (large excess of 2M solution in diethyl ether)
  10. stirringthe mixture stirred
  11. customThen all the volatiles were evaporated in vacuo

Sources & evidence

ORD record
ord-dfa4b27d43044f6e80bbf139518996ea
Source dataset
uspto-grants-2008_04
Patent number
US07354920B2

Reaction notes

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