2,2,2-Trichloro-tert-butyl chloroformate → (rac.)-(1R*,5S*)-7-{6-[2-(2,6-Dichloro-4-methyl-phenoxy)-ethoxy]-pyridin-3-yl}-3,9-diaza-bicyclo[3.3.1]non-6-ene-3,6,9-tricarboxylic Acid 3-tert-butyl Ester 6-ethyl Ester 9-(2,2,2-trichloro-1,1-dimethyl-ethyl) Ester

HRID 2428180Notes

Reaction equation

HRID 2428180 reaction equation
Cl[C:2]([O:4][C:5]([CH3:11])([CH3:10])[C:6]([Cl:9])([Cl:8])[Cl:7])=[O:3].[CH2:12]([O:14][C:15]([C:17]1[C@@H:18]2[N:44](C)[C@H:22]([CH2:23][C:24]=1[C:25]1[CH:26]=[N:27][C:28]([O:31][CH2:32][CH2:33][O:34][C:35]3[C:40]([Cl:41])=[CH:39][C:38]([CH3:42])=[CH:37][C:36]=3[Cl:43])=[CH:29][CH:30]=1)[CH2:21][N:20]([C:46]([O:48][C:49]([CH3:52])([CH3:51])[CH3:50])=[O:47])[CH2:19]2)=[O:16])[CH3:13]>>[Cl:7][C:6]([Cl:9])([Cl:8])[C:5]([O:4][C:2]([N:44]1[C@H:18]2[C:17]([C:15]([O:14][CH2:12][CH3:13])=[O:16])=[C:24]([C:25]3[CH:26]=[N:27][C:28]([O:31][CH2:32][CH2:33][O:34][C:35]4[C:40]([Cl:41])=[CH:39][C:38]([CH3:42])=[CH:37][C:36]=4[Cl:43])=[CH:29][CH:30]=3)[CH2:23][C@@H:22]1[CH2:21][N:20]([C:46]([O:48][C:49]([CH3:50])([CH3:52])[CH3:51])=[O:47])[CH2:19]2)=[O:3])([CH3:11])[CH3:10]

Participants

3

Reactant 2

HCID 51066062,2,2-Trichloro-tert-butyl chloroformate2×HCID 131728972(rac.)-(1R*,5S*)-7-{6-[2-(2,6-Dichloro-4-methyl-phenoxy)-ethoxy]-pyridin-3-yl}-9-methyl-3,9-diaza-bicyclo[3.3.1]non-6-ene-3,6-dicarboxylic Acid 3-tert-butyl Ester 6-ethyl Ester

Product 1

HCID 131728973(rac.)-(1R*,5S*)-7-{6-[2-(2,6-Dichloro-4-methyl-phenoxy)-ethoxy]-pyridin-3-yl}-3,9-diaza-bicyclo[3.3.1]non-6-ene-3,6,9-tricarboxylic Acid 3-tert-butyl Ester 6-ethyl Ester 9-(2,2,2-trichloro-1,1-dimethyl-ethyl) EsterYield 44.3%

Procedure

2,2,2-Trichloro-1,1-dimethylethyl chloroformate (2.77 g, 11.6 mmol) was added to a sol. of compound C4 (1.40 g, 2.31 mmol) in CH2ClCH2Cl (30 mL), and the mixture was heated to reflux for 2 h. 2,2,2-Trichloro-1,1-dimethylethyl chloroformate (1.40 g, 5.5 mmol) was added again, and the mixture was heated to reflux for 2 h. The mixture was allowed to cool to rt, and the solvents were removed under reduced pressure. The residue was diluted with EtOAc, and washed with aq. 1M NaOH (2×). The combined aq. layers were extracted back with EtOAc (2×). The combined org. extracts were dried over MgSO4, filtered, and the solvents were removed under reduced pressure. Purification of the residue by FC (EtOAc/heptane 1:4) yielded the title compound (815 mg, 44%). LC-MS: tR=1.25 min; ES+: 796.32.

Workup

  1. temperaturethe mixture was heated
  2. temperatureto reflux for 2 h
  3. temperaturethe mixture was heated
  4. temperatureto reflux for 2 h
  5. customthe solvents were removed under reduced pressure
  6. additionThe residue was diluted with EtOAc
  7. washwashed with aq. 1M NaOH (2×)
  8. extractionThe combined aq. layers were extracted back with EtOAc (2×)
  9. dry with materialextracts were dried over MgSO4
  10. filtrationfiltered
  11. customthe solvents were removed under reduced pressure
  12. customPurification of the residue by FC (EtOAc/heptane 1:4)

Sources & evidence

ORD record
ord-bc2db18926ec4d1296a277afc6bc6980
Source dataset
uspto-grants-2011_06
Patent number
US07968720B2

Reaction notes

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