Oxalyl chloride → HCID 86730038, compound

HRID 2199469Notes

Reaction equation

HRID 2199469 reaction equation
[O:1]=[C:2]1[O:6][CH2:5][C@:4]2([CH2:10][CH2:9][C@H:8]([C:11]3[CH:16]=[CH:15][C:14]([CH2:17][C:18](O)=[O:19])=[CH:13][CH:12]=3)[CH2:7]2)[NH:3]1.[C:21](Cl)(=O)[C:22](Cl)=O.[Cl-].[Al+3].[Cl-].[Cl-]>C(Cl)Cl.CN(C=O)C>[O:19]=[C:18]1[CH2:22][CH2:21][C:15]2[CH:16]=[C:11]([C@H:8]3[CH2:9][CH2:10][C@@:4]4([NH:3][C:2](=[O:1])[O:6][CH2:5]4)[CH2:7]3)[CH:12]=[CH:13][C:14]=2[CH2:17]1

Participants

6

Reactant 3

HCID 65578Oxalyl chlorideHCID 6451240Aluminum(III) ChlorideHCID 86730037HCID 86730037, compound

Product 1

HCID 86730038HCID 86730038, compoundYield 92.7%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
-78 °C

Procedure

To a mixture of 2-(4-((5R,7S)-2-oxo-3-oxa-1-azaspiro[4.4]nonan-7-yl)phenyl)acetic acid (I-5B, 800 mg, 2.91 mmol) in DCM (20 mL) was added oxalyl chloride (1 ml, 11.42 mmol) and a few drops of DMF. After one hour, the reaction mixture was concentrated in vacuo. The residue was re-dissolved in DCM (20 mL) in a glass pressure vessel. Granular aluminum chloride (1550 mg, 11.62 mmol) was added and the reaction mixture was cooled to −78° C. Ethylene was bubbled through the solution for 5 minutes and then the reaction vessel was sealed. The reaction mixture was allowed to slowly warm to room temperature and stirred for 4 hours. The mixture was poured onto ice, diluted with dichloromethane and washed with 1M HCl. The organic layer was dried with MgSO4, filtered and concentrated. The crude material was purified on a silica gel cartridge (80 g) using a MeOH/DCM gradient (0-10% MeOH over 13 CV). The product containing fractions were collected and dried in vacuo to afford 770 mg of (5R,7S)-7-(6-oxo-5,6,7,8-tetrahydronaphthalen-2-yl)-3-oxa-1-azaspiro[4.4]nonan-2-one. HPLC retention time=0.74 min (Condition G); LC/MS M+1=286: 1H NMR (400 MHz, chloroform-d) δ 7.20-7.00 (m, 3H), 5.49 (br. s., 1H), 4.45-4.25 (m, 2H), 3.59 (s, 2H), 3.08 (t, J=6.8 Hz, 3H), 2.58 (t, J=6.7 Hz, 2H), 2.38 (dd, J=13.2, 7.3 Hz, 1H), 2.27-2.11 (m, 2H), 2.05-1.92 (m, 2H), 1.92-1.74 (m, 1H).

Workup

  1. concentrationthe reaction mixture was concentrated in vacuo
  2. dissolutionThe residue was re-dissolved in DCM (20 mL) in a glass pressure vessel
  3. customEthylene was bubbled through the solution for 5 minutes
  4. customthe reaction vessel was sealed
  5. temperatureto slowly warm to room temperature
  6. additionThe mixture was poured onto ice
  7. additiondiluted with dichloromethane
  8. washwashed with 1M HCl
  9. dry with materialThe organic layer was dried with MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customThe crude material was purified on a silica gel cartridge (80 g)
  13. additionThe product containing fractions
  14. customwere collected
  15. customdried in vacuo

Sources & evidence

ORD record
ord-457c52fe8dcd494d98e159b85115f814
Source dataset
uspto-grants-2016_06
Patent number
US09359286B2

Reaction notes

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