Diisobutylaluminumhydride → 5-(6-Dihydroxymethyl-pyrimidin-4-yloxy)-2,3-dihydro-indole-1-carboxylic acid (3-trifluoromethyl-phenyl)-amide

HRID 2264614Notes

Reaction equation

HRID 2264614 reaction equation
C([O:3][C:4]([C:6]1[CH:11]=[C:10]([O:12][C:13]2[CH:14]=[C:15]3[C:19](=[CH:20][CH:21]=2)[N:18]([C:22](=[O:34])[NH:23][C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([C:30]([F:33])([F:32])[F:31])[CH:25]=2)[CH2:17][CH2:16]3)[N:9]=[CH:8][N:7]=1)=[O:5])C.[H-].C([Al+]CC(C)C)C(C)C>C1COCC1.CCOC(C)=O.O>[F:32][C:30]([F:31])([F:33])[C:26]1[CH:25]=[C:24]([NH:23][C:22]([N:18]2[C:19]3[C:15](=[CH:14][C:13]([O:12][C:10]4[CH:11]=[C:6]([CH:4]([OH:5])[OH:3])[N:7]=[CH:8][N:9]=4)=[CH:21][CH:20]=3)[CH2:16][CH2:17]2)=[O:34])[CH:29]=[CH:28][CH:27]=1

Participants

6

Reactant 2

HCID 21225700DiisobutylaluminumhydrideHCID 675312166-[1-(3-trifluoromethyl-phenylcarbamoyl)-2,3-dihydro-1H-indol-5-yloxy]-pyrimidine-4-carboxylic acid ethyl ester

Product 1

HCID 595963845-(6-Dihydroxymethyl-pyrimidin-4-yloxy)-2,3-dihydro-indole-1-carboxylic acid (3-trifluoromethyl-phenyl)-amide

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To solution of 100 mg (0.21 mMol) 6-[1-(3-trifluoromethyl-phenylcarbamoyl)-2,3-dihydro-1H-indol-5-yloxy]-pyrimidine-4-carboxylic acid ethyl ester (Expl. 72) in 3 ml THF at −78° C. are added 1.39 ml of a 1 M solution of diisobutylaluminium hydride in THF. After 20 h at −78° C., the mixture is slowly warmed up to 0° C. and stirred at this temperature for 2 h. Then the mixture is diluted with EtOAc and water, the aqueous layer separeted off and extracted twice with EtOAc. The organic phases are washed with water and brine, dried (Na2SO4) and after addition of 0.25 g of SiO2 concentrated. The resulting powder is put on top of a chromatography column (SiO2; EtOAc/hexane 1:4) and the title compound eluated with EtOAc/hexane 1:1: MS: [M+1]+=446; HPLC: AtRet=13.0.

Workup

  1. extractionextracted twice with EtOAc
  2. washThe organic phases are washed with water and brine
  3. dry with materialdried (Na2SO4)
  4. additionafter addition of 0.25 g of SiO2
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-4b9001ac709f4f7289f6af0da699cdda
Source dataset
uspto-grants-2010_12
Patent number
US07855215B2

Reaction notes

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