Diisopropylethylamine → N-(4-(3-((tert-butyldimethylsilyl)oxy)-2,2-dimethylpropyl)-3-(trifluoromethyl)phenyl)-2-(3-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)acetamide

HRID 1050141Notes

Reaction equation

HRID 1050141 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH2:17][C:18](O)=[O:19])[CH:5]=[CH:6][C:7]=1[B:8]1[O:12][C:11]([CH3:14])([CH3:13])[C:10]([CH3:16])([CH3:15])[O:9]1.[Si:21]([O:28][CH2:29][C:30]([CH3:44])([CH3:43])[CH2:31][C:32]1[CH:38]=[CH:37][C:35]([NH2:36])=[CH:34][C:33]=1[C:39]([F:42])([F:41])[F:40])([C:24]([CH3:27])([CH3:26])[CH3:25])([CH3:23])[CH3:22].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(Cl)Cl>[Si:21]([O:28][CH2:29][C:30]([CH3:44])([CH3:43])[CH2:31][C:32]1[CH:38]=[CH:37][C:35]([NH:36][C:18](=[O:19])[CH2:17][C:4]2[CH:5]=[CH:6][C:7]([B:8]3[O:12][C:11]([CH3:13])([CH3:14])[C:10]([CH3:16])([CH3:15])[O:9]3)=[C:2]([F:1])[CH:3]=2)=[CH:34][C:33]=1[C:39]([F:40])([F:41])[F:42])([C:24]([CH3:27])([CH3:26])[CH3:25])([CH3:23])[CH3:22]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 754871622-(3-Fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)acetic acidHCID 904158574-(3-((Tert-butyldimethylsilyl)oxy)-2,2-dimethylpropyl)-3-(trifluoromethyl)aniline

Product 1

HCID 90422972N-(4-(3-((tert-butyldimethylsilyl)oxy)-2,2-dimethylpropyl)-3-(trifluoromethyl)phenyl)-2-(3-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)acetamideYield 72%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
25 °C

Procedure

To a solution of 2-(3-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)acetic acid (5 g, 17.85 mmol) in DCM (100 mL) was added 4-(3-((tert-butyldimethylsilyl)oxy)-2,2-dimethylpropyl)-3-(trifluoromethyl)aniline (7.10 g, 19.64 mmol), DIEA (6.24 mL, 35.7 mmol) and HATU (8.14 g, 21.42 mmol). The solution was stirred at 25° C. for 16 h. Then the reaction mixture was concentrated to give the crude product, which was purified by silica column chromatography (PE/EA=8:1). All fractions found to contain product by TLC (PE/EA=8:1, Rf=0.6) were combined and concentrated to yield a white solid of N-(4-(3-((tert-butyldimethylsilyl)oxy)-2,2-dimethylpropyl)-3-(trifluoromethyl)phenyl)-2-(3-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)acetamide (10 g, 12.83 mmol, 72% yield): 1H NMR (400 MHz, CD3OD) δ 7.83 (d, J=2.0 Hz, 2H), 7.35 (d, J=8.8 Hz, 2H), 6.99 (dd, J=4.8, 10.0 Hz, 2H), 3.63 (s, 2H), 3.26 (s, 2H), 2.69 (s, 2H), 1.11 (s, 12H), 0.86 (s, 9H), 0.73 (s, 6H), 0.00 (s, 6H); ES-LCMS m/z 624.2 (M+H).

Workup

  1. concentrationThen the reaction mixture was concentrated
  2. customto give the crude product, which
  3. customwas purified by silica column chromatography (PE/EA=8:1)
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-86d0c47c638f4504a621e948a3917ab9
Source dataset
uspto-grants-2016_07
Patent number
US09382238B2

Reaction notes

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