Acetic Acid → HCID 52935018, compound

HRID 2041709Notes

Reaction equation

HRID 2041709 reaction equation
[CH3:1][CH:2]([O:4][C:5](=[O:29])[NH:6][C@H:7]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([C:17]3[CH:22]=[CH:21][C:20]([CH:23]=O)=[CH:19][CH:18]=3)[CH:15]=2)[N:10]([C:25](=[O:27])[CH3:26])[C@@H:9]([CH3:28])[CH2:8]1)[CH3:3].C(O)(=O)C.[NH:34]1[CH2:39][CH2:38][CH2:37][CH2:36][CH2:35]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl.CO>[NH3:6].[C:25]([N:10]1[C:11]2[C:16](=[CH:15][C:14]([C:17]3[CH:18]=[CH:19][C:20]([CH2:23][N:34]4[CH2:39][CH2:38][CH2:37][CH2:36][CH2:35]4)=[CH:21][CH:22]=3)=[CH:13][CH:12]=2)[C@H:7]([NH:6][C:5](=[O:29])[O:4][CH:2]([CH3:3])[CH3:1])[CH2:8][C@@H:9]1[CH3:28])(=[O:27])[CH3:26]

Participants

8

Reactant 4

HCID 176Acetic AcidHCID 8082PiperidineHCID 5049666Sodium triacetoxyborohydrideHCID 86669228HCID 86669228, compound

Product 2

HCID 222AmmoniaHCID 52935018HCID 52935018, compoundYield 68.9%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent2×

Procedure

A suspension of 1-methylethyl[(2S,4R)-1-acetyl-6-(4-formylphenyl)-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl]carbamate (for a preparation see Intermediate 68) (1.078 g, 2.73 mmol) in dichloromethane (DCM) (20 mL) under nitrogen was treated with acetic acid (0.313 mL, 5.47 mmol) and piperidine (0.279 g, 3.28 mmol). The resulting mixture was stirred at room temperature for 1 h then sodium triacetoxyborohydride (0.695 g, 3.28 mmol) was added and the reaction left to stir at room temperature over 60 h then concentrated in vacuovacuo. The residue was partitioned between a saturated NaHCO3 aqueous solution (25 mL) and AcOEt (40 mL) and the layers were separated. The aqueous phase was extracted with AcOEt (25 mL) and the combined organic phases were washed with brine, dried over Na2SO4 and concentrated in vacuovacuo. The residue was loaded on a 20 g SCX cartridge and eluted with MeOH (45 mL) then with 2M NH3 in MeOH (2×45 mL). The ammonia fractions were combined and concentrated in vacuo to give a first residue. The methanol fractions were concentrated and the residue obtained was loaded on a 20 g SCX cartridge and eluted with MeOH (45 mL) then with 2M NH3 in MeOH (2×45 mL). The ammonia fractions were combined and concentrated in vacuo to give a second residue. The two residues were combined and purified by flash chromatography on silica gel using an SP4 and a 100 G cartridge (gradient:1 to 5% (2M NH3 in MeOH) in DCM) to give 1-methylethyl {(2S,4R)-1-acetyl-2-methyl-6-[4-(1-piperidinylmethyl)phenyl]-1,2,3,4-tetrahydro-4-quinolinyl}carbamate (0.9195 g, 1.884 mmol, 68.9% yield) as a yellow oil.

Workup

  1. waitthe reaction left
  2. stirringto stir at room temperature over 60 h
  3. concentrationthen concentrated in vacuovacuo
  4. customThe residue was partitioned between a saturated NaHCO3 aqueous solution (25 mL) and AcOEt (40 mL)
  5. customthe layers were separated
  6. extractionThe aqueous phase was extracted with AcOEt (25 mL)
  7. washthe combined organic phases were washed with brine
  8. dry with materialdried over Na2SO4
  9. concentrationconcentrated in vacuovacuo
  10. washeluted with MeOH (45 mL)
  11. concentrationconcentrated in vacuo
  12. customto give a first residue
  13. concentrationThe methanol fractions were concentrated
  14. customthe residue obtained
  15. washeluted with MeOH (45 mL)
  16. concentrationconcentrated in vacuo
  17. customto give a second residue
  18. custompurified by flash chromatography on silica gel using an SP4

Sources & evidence

ORD record
ord-1c08e472ee7240eabc5cbfbb6e082c16
Source dataset
uspto-grants-2013_11
Patent number
US08580957B2

Reaction notes

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