تفاعل #160197

معادلة التفاعل

1-Chloroethyl carbonochloridate

[8-benzyl-10-(4-chlorophenyl)-11-oxa-3,8-diazaspiro[5.5]undecan-3-yl]-(4-isopropoxy-3-methyl-phenyl)methanone

→

[10-(4-chlorophenyl)-11-oxa-3,8-diazaspiro[5.5]undecan-3-yl]-(4-isopropoxy-3-methyl-phenyl)methanone

المردود 62.1%

المذيبات

DCE

ظروف التفاعل

المعالجة

1. 1
   درجة الحرارةthe reaction mixture was heated
2. 2
   درجة الحرارةat reflux for 1 hour
3. 3
   أخرىThe excess solvent was removed in vacuo
4. 4
   workup.DISSOLUTIONthe carbamate intermediate was dissolved in MeOH (2 mL)
5. 5
   درجة الحرارةheated
6. 6
   درجة الحرارةat reflux for 20 minutes
7. 7
   ترشيحfiltered
8. 8
   أخرىpurified by Waters mass
9. 9
   تركيزThe desired fractions were concentrated to dryness
10. 10
    workup.DISSOLUTIONdissolved in EtOAc
11. 11
    غسيلwashed with 1M NaOH
12. 12
    تجفيفThe combined organics were dried over Na2SO4
13. 13
    ترشيحfiltered
14. 14
    تركيزconcentrated in vacuo

الإجراء التجريبي

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)

المصدر