Sodium hydride → (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

HRID 661454Notes

Reaction equation

HRID 661454 reaction equation
[C:1]([O:5][C:6](=[O:12])[C:7]([CH3:11])([CH3:10])[CH2:8][OH:9])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[N+](C1C=CC([O:24][C:25]([N:27]2[C:36]3[C:31](=[CH:32][C:33]([C:37]([F:40])([F:39])[F:38])=[CH:34][CH:35]=3)[C@@H:30]([NH:41][C:42]3[CH:47]=[CH:46][C:45]([N:48]4[CH2:53][CH2:52][O:51][CH2:50][CH2:49]4)=[CH:44][N:43]=3)[CH2:29][C@H:28]2[CH2:54][CH3:55])=O)=CC=1)([O-])=O.C(=O)([O-])O.[Na+]>O1CCCC1.C(OCC)(=O)C>[C:1]([O:5][C:6]([C:7]([CH3:11])([CH3:10])[CH2:8][O:9][C:25]([N:27]1[C:36]2[C:31](=[CH:32][C:33]([C:37]([F:40])([F:38])[F:39])=[CH:34][CH:35]=2)[C@@H:30]([NH:41][C:42]2[CH:47]=[CH:46][C:45]([N:48]3[CH2:49][CH2:50][O:51][CH2:52][CH2:53]3)=[CH:44][N:43]=2)[CH2:29][C@H:28]1[CH2:54][CH3:55])=[O:24])=[O:12])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 516892Sodium BicarbonateHCID 54272639Tert-butyl 3-hydroxy-2,2-dimethylpropanoateHCID 57972843(2R,4S)-2-Ethyl-4-(5-morpholin-4-yl-pyridin-2-ylamino)-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid 4-nitrophenyl ester

Product 1

HCID 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 esterYield 71.3%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

3-Hydroxy-2,2-dimethyl-propionic acid tert-butyl ester (137 mg) and sodium hydride (60%; 32 mg) were added to a solution of the compound obtained in Example 9 (1) (300 mg) dissolved in tetrahydrofuran (5 ml) and stirred at 50° C. for 2 hours. The reaction mixture was cooled to room temperature, a saturated sodium hydrogen carbonate aq. solution and ethyl acetate were added 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=7:3→2:3) to give the titled compound (227 mg). MS (m/z):607 [M+H]+.

Workup

  1. temperatureThe reaction mixture was cooled 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=7:3→2:3)

Sources & evidence

ORD record
ord-e80c36a2a2f545839918a8032f5c1453
Source dataset
uspto-grants-2011_12
Patent number
US08084611B2

Reaction notes

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