Hydrochloric Acid → (2R,4S)-4-[(3,5-Bis-trifluoromethyl-benzyl)-(5-morpholin-4-yl-pyridin-2-yl)-amino]-2-ethyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid 2-tert-butoxycarbonyl-2-methyl-propyl ester

HRID 661455Notes

Reaction equation

HRID 661455 reaction equation
[C:1]([O:5][C:6]([C:8]([CH3:43])([CH3:42])[CH2:9][O:10][C:11]([N:13]1[C:22]2[C:17](=[CH:18][C:19]([C:23]([F:26])([F:25])[F:24])=[CH:20][CH:21]=2)[C@@H:16]([NH:27][C:28]2[CH:33]=[CH:32][C:31]([N:34]3[CH2:39][CH2:38][O:37][CH2:36][CH2:35]3)=[CH:30][N:29]=2)[CH2:15][C@H:14]1[CH2:40][CH3:41])=[O:12])=[O:7])([CH3:4])([CH3:3])[CH3:2].[F:44][C:45]([F:59])([F:58])[C:46]1[CH:47]=[C:48]([CH:51]=[C:52]([C:54]([F:57])([F:56])[F:55])[CH:53]=1)[CH2:49]Br.Cl.C(OCC)(=O)C>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.COC(C)(C)C>[C:1]([O:5][C:6]([C:8]([CH3:42])([CH3:43])[CH2:9][O:10][C:11]([N:13]1[C:22]2[C:17](=[CH:18][C:19]([C:23]([F:25])([F:24])[F:26])=[CH:20][CH:21]=2)[C@@H:16]([N:27]([CH2:49][C:48]2[CH:51]=[C:52]([C:54]([F:56])([F:57])[F:55])[CH:53]=[C:46]([C:45]([F:44])([F:58])[F:59])[CH:47]=2)[C:28]2[CH:33]=[CH:32][C:31]([N:34]3[CH2:35][CH2:36][O:37][CH2:38][CH2:39]3)=[CH:30][N:29]=2)[CH2:15][C@H:14]1[CH2:40][CH3:41])=[O:12])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 8857Ethyl AcetateHCID 1225733,5-Bis(trifluoromethyl)benzyl bromideHCID 67141613(2R,4S)-2-Ethyl-4-(5-morpholin-4-yl-pyridin-2-ylamino)-6-trifluoromethyl-3,4-dihydro-2H-quinolin-1-carboxylic acid 2-tert-butoxycarbonyl-2-methyl-propyl ester

Product 1

HCID 86636544(2R,4S)-4-[(3,5-Bis-trifluoromethyl-benzyl)-(5-morpholin-4-yl-pyridin-2-yl)-amino]-2-ethyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid 2-tert-butoxycarbonyl-2-methyl-propyl ester

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 15413tert-Butyl methyl etherSolvent

Procedure

Tetrabutylammonium iodide (53 mg) was added to a solution of the compound obtained in Example 9 (2) above (217 mg) in tert-butyl methyl ether (4 ml) under nitrogen atmosphere at 0° C. 3,5-Bis(trifluoromethyl)benzyl bromide (164 mg) was added dropwise and the solution was stirred for 4.5 hours while the temperature was gradually raised from 0° C. to room temperature. To the reaction mixture, were added with 1N hydrochloric acid and ethyl acetate, and the organic layer was separated, washed with a saturated brine, dried over magnesium sulfate and concentrated in vacuo. The resulting residue was purified by column chromatography (silica gel; hexane:ethyl acetate=19:1→4:1) to give the titled compound (182 mg). MS (m/z): 833 [M+H]+.

Workup

  1. temperaturewas gradually raised from 0° C. to room temperature
  2. customthe organic layer was separated
  3. washwashed with a saturated brine
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe resulting residue was purified by column chromatography (silica gel; hexane:ethyl acetate=19:1→4:1)

Sources & evidence

ORD record
ord-551379d53cb74b7d917372d840929971
Source dataset
uspto-grants-2011_12
Patent number
US08084611B2

Reaction notes

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