Ethyl Acetate → HCID 90423309, compound

HRID 1050183Notes

Reaction equation

HRID 1050183 reaction equation
[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([C:20]2[CH:25]=[CH:24][C:23]([CH2:26][C:27]([NH:29][C:30]3[CH:35]=[CH:34][C:33]([CH2:36][C:37]([F:44])([F:43])[C:38](OCC)=[O:39])=[C:32]([C:45]([F:48])([F:47])[F:46])[CH:31]=3)=[O:28])=[C:22]([F:49])[CH:21]=2)[CH:7]=[N:8][C:9]=1[O:10][CH2:11][C:12]1[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][CH:13]=1)[CH3:2].[H-].[H-].[H-].[H-].[Li+].[Al+3].CC(=O)OCC>C1COCC1>[F:44][C:37]([F:43])([CH2:38][OH:39])[CH2:36][C:33]1[CH:34]=[CH:35][C:30]([NH:29][C:27](=[O:28])[CH2:26][C:23]2[CH:24]=[CH:25][C:20]([C:6]3[CH:7]=[N:8][C:9]([O:10][CH2:11][C:12]4[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][CH:13]=4)=[C:4]([O:3][CH2:1][CH3:2])[CH:5]=3)=[CH:21][C:22]=2[F:49])=[CH:31][C:32]=1[C:45]([F:46])([F:47])[F:48]

Participants

5

Reactant 3

HCID 8857Ethyl AcetateHCID 21226445Aluminium lithium hydrideHCID 90423010HCID 90423010, compound

Product 1

HCID 90423309HCID 90423309, compoundYield 71.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of ethyl 3-(4-(2-(4-(5-ethoxy-6-((4-methoxybenzyl)oxy)pyridin-3-yl)-2-fluorophenyl)acetamido)-2-(trifluoromethyl)phenyl)-2,2-difluoropropanoate (100 mg, 0.145 mmol) in THF (5 mL) was added LAH (5.50 mg, 0.145 mmol) at 0° C. The mixture was stirred for 1 h. LCMS and TLC (PE/EA=1:1, Rf=0.2) showed the reaction was finished. The reaction was quenched by water (0.3 mL). The mixture was filtered, and the filtrate was concentrated to give N-(4-(2,2-difluoro-3-hydroxypropyl)-3-(trifluoromethyl)phenyl)-2-(4-(5-ethoxy-6-((4-methoxybenzyl)oxy)pyridin-3-yl)-2-fluorophenyl)acetamide (80 mg, 0.104 mmol, 71.6% yield): 1H NMR (400 MHz, CD3OD-d4) δ 8.01 (s, 1H), 7.94 (d, J=2.0 Hz, 1H), 7.77 (d, J=8.6 Hz, 1H), 7.52 (d, J=8.8 Hz, 1H), 7.47-7.27 (m, 6H), 6.90 (d, J=8.8 Hz, 2H), 5.35 (s, 2H), 4.22-4.11 (m, 2H), 3.82-3.75 (m, 3H), 3.67 (t, J=13.0 Hz, 2H), 3.47-3.37 (m, 2H), 3.37-3.34 (m, 2H), 1.41 (t, J=7.1 Hz, 3H). ES-LCMS m/z 649 (M+H).

Workup

  1. customThe reaction was quenched by water (0.3 mL)
  2. filtrationThe mixture was filtered
  3. concentrationthe filtrate was concentrated

Sources & evidence

ORD record
ord-b1b88fa875224cc99453ca71c2ebe8b6
Source dataset
uspto-grants-2016_07
Patent number
US09382238B2

Reaction notes

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