Acetic Acid → HCID 22380643, compound

HRID 1922448Notes

Reaction equation

HRID 1922448 reaction equation
[NH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][CH2:2]1.O=[C:12]1[CH2:17][CH2:16][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:14][CH2:13]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O)(=O)C>ClCCCl>[N:1]1([CH:12]2[CH2:17][CH2:16][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:14][CH2:13]2)[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 694601,2,3,4-Tetrahydroquinoline2×HCID 735900tert-Butyl 4-oxopiperidine-1-carboxylate2×HCID 5049666Sodium triacetoxyborohydride2×

Product 1

HCID 22380643HCID 22380643, compoundYield 37.5%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

A solution of 1,2,3,4-tetrahydroquinoline (1.06 g, 7.51 mmol) and tert-butyl 4-oxopiperidine-1-carboxylate (2.24 g, 11.26 mmol) in 20 mL 1,2-dichloroethane was treated with sodium triacetoxyborohydride (4.77 g, 22.53 mmol) then acetic acid (1.28 mL, 22.53 mmol). The suspension was stirred at room temperature overnight. At this time, a TLC analysis indicated that 1,2,3,4-tetrahydroquinoline is present along with a more polar spot. To the reaction mixture was added tert-butyl 4-oxopiperidine-1-carboxylate (1.12 g, 5.63 mmol) and sodium triacetoxyborohydride (2.39 g, 11.28 mmol). The suspension was stirred at room temperature for 4 days. After this time, the mixture was cooled to 0° C., quenched with 20 mL 1N NaOH and stirred for 20 minutes. The organic layer was separated and the aqueous layer was extracted with 50 mL CH2Cl2. The combined organic layer was dried over Na2SO4, filtered and concentrated to give a yellow residue. This residue was purified by the Biotage purification system using a silica gel 40M column. A gradient of 5% ethyl acetate:hexanes to 30% ethyl acetate:hexanes over 10 column volumes was used to give the title compound (0.89 g, 37.4%). 1H-NMR (CDCl3) δ 7.09-7.03 (m, 1H), 6.97-6.94 (m, 1H), 6.65 (d, J=8.4 Hz, 1H), 6.60-6.55 (m, 1H), 4.30-4.19 (m, 2H), 3.80-3.70 (m, 1H), 3.17 (t, J=5.7 Hz, 2H), 2.84-2.71 (m, 2H), 2.73 (t, J=6.3 Hz, 2H), 1.93-1.85 (m, 2H), 1.78-1.63 (m, 4H), 1.48 (s, 9H). MS (ESI): 317.2 (M+1).

Workup

  1. stirringThe suspension was stirred at room temperature for 4 days
  2. temperatureAfter this time, the mixture was cooled to 0° C.
  3. customquenched with 20 mL 1N NaOH
  4. stirringstirred for 20 minutes
  5. customThe organic layer was separated
  6. extractionthe aqueous layer was extracted with 50 mL CH2Cl2
  7. dry with materialThe combined organic layer was dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customto give a yellow residue
  11. customThis residue was purified by the Biotage purification system

Sources & evidence

ORD record
ord-d4ec1136bd96498b8cb410c6cf894694
Source dataset
uspto-grants-2012_05
Patent number
US08173813B2

Reaction notes

Loading…