1-Chloroethyl chloroformate → [10-(4-Chlorophenyl)-11-oxa-3,8-diazaspiro[5.5]undecan-3-yl]-(4-isopropoxy-3-methyl-phenyl)methanone

HRID 73015Notes

Reaction equation

HRID 73015 reaction equation
C(Cl)(=O)OC(Cl)C.C([N:15]1[CH2:38][CH:37]([C:39]2[CH:44]=[CH:43][C:42]([Cl:45])=[CH:41][CH:40]=2)[O:36][C:17]2([CH2:22][CH2:21][N:20]([C:23]([C:25]3[CH:30]=[CH:29][C:28]([O:31][CH:32]([CH3:34])[CH3:33])=[C:27]([CH3:35])[CH:26]=3)=[O:24])[CH2:19][CH2:18]2)[CH2:16]1)C1C=CC=CC=1>ClCCCl>[Cl:45][C:42]1[CH:43]=[CH:44][C:39]([CH:37]2[O:36][C:17]3([CH2:18][CH2:19][N:20]([C:23]([C:25]4[CH:30]=[CH:29][C:28]([O:31][CH:32]([CH3:33])[CH3:34])=[C:27]([CH3:35])[CH:26]=4)=[O:24])[CH2:21][CH2:22]3)[CH2:16][NH:15][CH2:38]2)=[CH:40][CH:41]=1

Participants

4

Reactant 2

HCID 5213051-Chloroethyl chloroformateHCID 70872873[8-Benzyl-10-(4-chlorophenyl)-11-oxa-3,8-diazaspiro[5.5]undecan-3-yl]-(4-isopropoxy-3-methyl-phenyl)methanone

Product 1

HCID 70872702[10-(4-Chlorophenyl)-11-oxa-3,8-diazaspiro[5.5]undecan-3-yl]-(4-isopropoxy-3-methyl-phenyl)methanoneYield 62.1%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

1-Chloroethyl carbonochloridate (142 mg, 108 μL, 0.99 mmol) was added to a solution of [8-benzyl-10-(4-chlorophenyl)-11-oxa-3,8-diazaspiro[5.5]undecan-3-yl]-(4-isopropoxy-3-methyl-phenyl)methanone (44 mg, 0.08 mmol) in DCE (508 μL) at room temperature and then the reaction mixture was heated at reflux for 1 hour. The excess solvent was removed in vacuo and the carbamate intermediate was dissolved in MeOH (2 mL) and heated at reflux for 20 minutes. The reaction mixture was cooled to room temperature, filtered and purified by Waters mass directed LC/MS-HPLC: (1-99% ACN/H2O (5 mM HCl)). The desired fractions were concentrated to dryness, dissolved in EtOAc and washed with 1M NaOH. The combined organics were dried over Na2SO4, filtered and concentrated in vacuo to yield [10-(4-chlorophenyl)-11-oxa-3,8-diazaspiro[5.5]undecan-3-yl]-(4-isopropoxy-3-methyl-phenyl)methanone (22 mg, 60%). ESI-MS m/z calc. 442.2. Found 443.5 (M+1)+; Retention time: 1.51 minutes (3 min run)

Workup

  1. temperaturethe reaction mixture was heated
  2. temperatureat reflux for 1 hour
  3. customThe excess solvent was removed in vacuo
  4. dissolutionthe carbamate intermediate was dissolved in MeOH (2 mL)
  5. temperatureheated
  6. temperatureat reflux for 20 minutes
  7. filtrationfiltered
  8. custompurified by Waters mass
  9. concentrationThe desired fractions were concentrated to dryness
  10. dissolutiondissolved in EtOAc
  11. washwashed with 1M NaOH
  12. dry with materialThe combined organics were dried over Na2SO4
  13. filtrationfiltered
  14. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-ab8088e7f86b48d8863970ecf2840044
Source dataset
uspto-grants-2014_09
Patent number
US08828996B2

Reaction notes

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