Hydrochloric Acid → (rac.)-(1R*,5S*)-3-Acetyl-7-{6-[2-(2,6-dichloro-4-methyl-phenoxy)-ethoxy]-pyridin-3-yl}-3,9-diaza-bicyclo[3.3.1]non-6-ene-6,9-dicarboxylic Acid 6-ethyl Ester 9-(2,2,2-trichloro-1,1-dimethyl-ethyl) Ester

HRID 2428184Notes

Reaction equation

HRID 2428184 reaction equation
Cl.[Cl:2][C:3]([Cl:51])([Cl:50])[C:4]([O:7][C:8]([N:10]1[C@H:15]2[C:16]([C:38]([O:40][CH2:41][CH3:42])=[O:39])=[C:17]([C:19]3[CH:20]=[N:21][C:22]([O:25][CH2:26][CH2:27][O:28][C:29]4[C:34]([Cl:35])=[CH:33][C:32]([CH3:36])=[CH:31][C:30]=4[Cl:37])=[CH:23][CH:24]=3)[CH2:18][C@@H:11]1[CH2:12][N:13]([C:43]([O:45]C(C)(C)C)=O)[CH2:14]2)=[O:9])([CH3:6])[CH3:5].[CH3:52]CN(C(C)C)C(C)C.C(Cl)(C)=O>C(Cl)Cl>[Cl:51][C:3]([Cl:50])([Cl:2])[C:4]([O:7][C:8]([N:10]1[C@H:15]2[C:16]([C:38]([O:40][CH2:41][CH3:42])=[O:39])=[C:17]([C:19]3[CH:20]=[N:21][C:22]([O:25][CH2:26][CH2:27][O:28][C:29]4[C:34]([Cl:35])=[CH:33][C:32]([CH3:36])=[CH:31][C:30]=4[Cl:37])=[CH:23][CH:24]=3)[CH2:18][C@@H:11]1[CH2:12][N:13]([C:43](=[O:45])[CH3:52])[CH2:14]2)=[O:9])([CH3:6])[CH3:5]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 6367Acetyl chlorideHCID 81531DiisopropylethylamineHCID 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) Ester

Product 1

HCID 131728974(rac.)-(1R*,5S*)-3-Acetyl-7-{6-[2-(2,6-dichloro-4-methyl-phenoxy)-ethoxy]-pyridin-3-yl}-3,9-diaza-bicyclo[3.3.1]non-6-ene-6,9-dicarboxylic Acid 6-ethyl Ester 9-(2,2,2-trichloro-1,1-dimethyl-ethyl) EsterYield 98%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

HCl (4M in dioxane, 30 mL) was added to a sol. of compound C5 (3.34 g, 4.20 mmol) in CH2Cl2 (30 mL) at 0° C. The mixture was stirred for 1 h at 0° C., then for 1 h at rt. The solvents were removed under reduced pressure, and the residue was dried under high vacuum. The residue was dissolved in CH2Cl2 (30 mL), and DIPEA (2.88 mL, 16.8 mmol) was added. The mixture was cooled to −20° C., and AcCl (0.315 mL, 4.41 mmol) was added carefully. The mixture was stirred for 20 min at −20° C., and CH2Cl2 was added. The mixture was washed with aq. 1M HCl and aq. 1M NaOH. The org. layer was dried over MgSO4, filtered, and the solvents were removed under reduced pressure. Purification of the residue by FC (EtOAc/heptane 1:4→1:3→1:2) yielded the title compound (3.03 g, 98%). LC-MS: tR=1.18 min; ES+: 738.14.

Workup

  1. waitfor 1 h at rt
  2. customThe solvents were removed under reduced pressure
  3. customthe residue was dried under high vacuum
  4. dissolutionThe residue was dissolved in CH2Cl2 (30 mL)
  5. temperatureThe mixture was cooled to −20° C.
  6. stirringThe mixture was stirred for 20 min at −20° C.
  7. washThe mixture was washed with aq. 1M HCl and aq. 1M NaOH
  8. dry with materiallayer was dried over MgSO4
  9. filtrationfiltered
  10. customthe solvents were removed under reduced pressure
  11. customPurification of the residue by FC (EtOAc/heptane 1:4→1:3→1:2)

Sources & evidence

ORD record
ord-0b45d67a9226439394f6042ff8a02889
Source dataset
uspto-grants-2011_06
Patent number
US07968720B2

Reaction notes

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