Hydrochloric Acid → 1-methylethyl((2S,4R)-1-acetyl-6-{4-[2-({[(1,1-dimethylethyl)oxy]carbonyl}amino)ethyl]phenyl}-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl)carbamate hydrochloride

HRID 2366956Notes

Reaction equation

HRID 2366956 reaction equation
FC(F)(F)[C:3]([OH:5])=[O:4].CC(OC(=O)[NH:13][C@H:14]1[C:23]2[C:18](=[CH:19][CH:20]=[C:21]([C:24]3[CH:29]=[CH:28][C:27]([CH2:30][CH2:31][NH:32][C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])=[CH:26][CH:25]=3)[CH:22]=2)[N:17]([C:40](=[O:42])[CH3:41])[C@@H:16]([CH3:43])[CH2:15]1)C.[C:45]1(C)[CH:50]=CC=C[CH:46]=1.[ClH:52]>ClCCl>[ClH:52].[CH3:46][CH:45]([N:13]([C@H:14]1[C:23]2[C:18](=[CH:19][CH:20]=[C:21]([C:24]3[CH:29]=[CH:28][C:27]([CH2:30][CH2:31][NH:32][C:33]([O:35][C:36]([CH3:37])([CH3:38])[CH3:39])=[O:34])=[CH:26][CH:25]=3)[CH:22]=2)[N:17]([C:40](=[O:42])[CH3:41])[C@@H:16]([CH3:43])[CH2:15]1)[C:3](=[O:4])[OH:5])[CH3:50]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 1140TolueneHCID 6422Trifluoroacetic acidHCID 681854061-methylethyl((2S,4R)-1-acetyl-6-{4-[2-({[(1,1-dimethylethyl)oxy]carbonyl}amino)ethyl]phenyl}-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl)carbamate

Product 1

HCID 671942101-methylethyl((2S,4R)-1-acetyl-6-{4-[2-({[(1,1-dimethylethyl)oxy]carbonyl}amino)ethyl]phenyl}-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl)carbamate hydrochlorideYield 80%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Trifluoroacetic acid (TFA) (3 mL) was added to a solution of 1-methylethyl((2S,4R)-1-acetyl-6-{4-[2-({[(1,1-dimethylethyl)oxy]carbonyl}amino)ethyl]phenyl}-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl)carbamate (for a preparation see Intermediate 87) (50 mg, 0.098 mmol) in dichloromethane (DCM) (3.00 mL) and the resulting mixture was stirred at room temperature under nitrogen for 3 h then concentrated in vacuo. The residue obtained was co-evaporated with toluene then purified using a SCX column (5 g, elution 5 column volume (CV) methanol, then 5 CV 2M NH3 in methanol). The ammonia fractions were collected and concentrated in vacuo to give a residue which was treated with HCl (1.0 M in Et2O, 2 mL, 2 mmol). The resulting mixture was concentrated in vacuo to give 1-methylethyl((2S,4R)-1-acetyl-6-{4-[2-({[(1,1-dimethylethyl)oxy]carbonyl}amino)ethyl]phenyl}-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl)carbamate hydrochloride (50 mg, 0.098 mmol, 80%) as a white solid.

Workup

  1. concentrationthen concentrated in vacuo
  2. customThe residue obtained
  3. customthen purified
  4. wash5 g, elution 5 column volume (CV) methanol
  5. customThe ammonia fractions were collected
  6. concentrationconcentrated in vacuo
  7. customto give a residue which
  8. concentrationThe resulting mixture was concentrated in vacuo

Sources & evidence

ORD record
ord-45da9ee9425c4ad8b4805fd36b08e5bd
Source dataset
uspto-grants-2014_04
Patent number
US08697725B2

Reaction notes

Loading…