1-Chloroethyl chloroformate → HCID 18782720, compound

HRID 1420686Notes

Reaction equation

HRID 1420686 reaction equation
[Cl:1]C(OC(Cl)C)=O.C([N:15]1[CH2:41][CH2:40][CH2:39][C:17]2([O:21][CH2:20][C:19]([C:22]3[CH:27]=[C:26]([N:28]4[C:32]([C:33]([F:36])([F:35])[F:34])=[N:31][N:30]=[N:29]4)[CH:25]=[CH:24][C:23]=3[O:37][CH3:38])=[CH:18]2)[CH2:16]1)C1C=CC=CC=1>ClCCl>[ClH:1].[CH3:38][O:37][C:23]1[CH:24]=[CH:25][C:26]([N:28]2[C:32]([C:33]([F:35])([F:36])[F:34])=[N:31][N:30]=[N:29]2)=[CH:27][C:22]=1[C:19]1[CH2:20][O:21][C:17]2([CH2:39][CH2:40][CH2:41][NH:15][CH2:16]2)[CH:18]=1

Participants

4

Reactant 2

HCID 5213051-Chloroethyl chloroformateHCID 18782698HCID 18782698, compound

Product 1

HCID 18782720HCID 18782720, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-4 °C

Procedure

1-Chloroethyl chloroformate (1.9 ml, 17.6 mmol) was added dropwise at 4° C. to a solution of 7-benzyl-3-(2-methoxy-5-(5-trifluoromethyl-1H-tetrazol-1-yl)phenyl)-1-oxa-7-azaspiro[4,5]dec-3-ene (free base of Ex. 2; 6.16 g, 13.07 mmol) in dichloromethane (60 ml). The reaction mixture was stirred at -4° C. for 30 minutes, allowed to warm to room temperature over 30 minutes and stirred at room temperature for 15 minutes. The reaction mixture was concentrated in vacuo, the residual red oil dissolved in methanol (60 ml) and heated at reflux for 40 minutes. The mixture was allowed to cool, concentrated in vacuo and the residue triturated with ether to give a title compound in two crops (3.54 g, 65%), m.p. 203°-205° C.; (Found: C, 48.33; H, 4.44; N, 16.31. C17H19ClF3N5O2. 0.25H2O requires C, 48.35; H, 4.65; N, 16.58%); δH (360MHz, DMSO-d6) 1.72-1.96 (4H, m), 2.85 (1H, m), 3.11 (3H, m), 4.00 (3H, s, ArOCH3), 4.99 (2H, m, 2-CH2, 6.64 (1H, br s, 4-CH=), 7.38 (1H, d, J 8.9Hz, 3'-H), 7.65 (1H, d, J 2.5Hz, 6'-H), 7.76 (1H, dd, J 8.9, 2.5Hz, 4'-H); m/z (ES+) 382 ([M+H]+).

Workup

  1. temperatureto warm to room temperature over 30 minutes
  2. stirringstirred at room temperature for 15 minutes
  3. concentrationThe reaction mixture was concentrated in vacuo
  4. dissolutionthe residual red oil dissolved in methanol (60 ml)
  5. temperatureheated
  6. temperatureat reflux for 40 minutes
  7. temperatureto cool
  8. concentrationconcentrated in vacuo
  9. customthe residue triturated with ether

Sources & evidence

ORD record
ord-e6e43b7c493f4072a1530d883f5ce10e
Source dataset
uspto-grants-2000_06
Patent number
US06071928

Reaction notes

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