Methanol → ethyl 4-((2S,4R)-1-acetyl-4-amino-2-methyl-1,2,3,4-tetrahydroquinolin-6-yl)benzoate

Temperature

0 °C

Ethyl 4-[(2S,4R)-1-acetyl-2-methyl-4-({[(1-methylethyl)oxy]carbonyl}amino)-1,2,3,4-tetrahydro-6-quinolinyl]benzoate (for a preparation see intermediate 53) (25.33 g, 57.8 mmol) was added to a cold (ice/water bath) suspension of aluminum chloride (29.24 g, 219 mmol) in DCM (450 mL). The resulting solution was stirred at approximately 0° C. for 35 min then a solution of triethylamine (96 mL, 693 mmol) and methanol (50 mL) was added over 30 s. The resulting mixture was stirred for approximately 1 h in the ice bath, and then partitioned between AcOEt and a saturated NaHCO3 aqueous solution. The mixture was filtered through Celite, and the residue washed with AcOEt and a saturated NaHCO3 aqueous solution (several times each). The layers were separated and the aqueous phase was extracted with AcOEt (×2). The combined organic phases were washed with brine, dried using a hydrophobic frit and concentrated in vacuovacuo. The solid obtained was dissolved, with warming, in AcOEt, filtered through Celite in order to remove remaining inorganics and the insoluble material was washed with warm AcOEt. The combined filtrate and washings were concentrated in vacuo to give a first batch of ethyl 4-[(2S,4R)-1-acetyl-4-amino-2-methyl-1,2,3,4-tetrahydro-6-quinolinyl]benzoate (15.0 g, 42.6 mmol, 74%) as a cream solid The solid residue on celite was further washed with acetone, and the filtrate concentrated in vacuovacuo. The residue was partially dissolved in AcOEt, filtered through a hydrophobic frit and the filtrate was concentrated vacuo to give a second batch of ethyl 4-[(2S,4R)-1-acetyl-4-amino-2-methyl-1,2,3,4-tetrahydro-6-quinolinyl]benzoate (2.78 g, 7.9 mmol, 14%) as a cream foam.

1. custompartitioned between AcOEt
2. filtrationThe mixture was filtered through Celite
3. washthe residue washed with AcOEt
4. customThe layers were separated
5. extractionthe aqueous phase was extracted with AcOEt (×2)
6. washThe combined organic phases were washed with brine
7. customdried
8. concentrationconcentrated in vacuovacuo
9. customThe solid obtained
10. dissolutionwas dissolved
11. filtrationfiltered through Celite in order
12. customto remove
13. washthe insoluble material was washed with warm AcOEt
14. concentrationThe combined filtrate and washings were concentrated in vacuo

ORD record

ord-801d3d0b683e4ef58b585809bf5b63bf

Source dataset

uspto-grants-2013_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08580957B2