Acetic Acid → N-(2-(3,5-dichloropyridin-4-yl)-2-((triethylsilyl)oxy)ethyl)-3,3,3-trifluoro-2,2-dim ethylpropan-1-amine

HRID 2202696Notes

Reaction equation

HRID 2202696 reaction equation
[Cl:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Cl:19])[C:7]=1[CH:8]([O:11][Si:12]([CH2:17][CH3:18])([CH2:15][CH3:16])[CH2:13][CH3:14])[CH2:9][NH2:10].[F:20][C:21]([F:28])([F:27])[C:22]([CH3:26])([CH3:25])[CH:23]=O.CC(O)=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Cl:19])[C:7]=1[CH:8]([O:11][Si:12]([CH2:15][CH3:16])([CH2:17][CH3:18])[CH2:13][CH3:14])[CH2:9][NH:10][CH2:23][C:22]([CH3:26])([CH3:25])[C:21]([F:28])([F:27])[F:20]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 5049666Sodium triacetoxyborohydrideHCID 599513523,3,3-Trifluoro-2,2-dimethylpropanalHCID 1236836992-(3,5-Dichloropyridin-4-yl)-2-((triethylsilyl)oxy)ethanamine

Product 1

HCID 123703112N-(2-(3,5-dichloropyridin-4-yl)-2-((triethylsilyl)oxy)ethyl)-3,3,3-trifluoro-2,2-dim ethylpropan-1-amineYield 69.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a yellow clear mixture of 2-(3,5-dichloropyridin-4-yl)-2-((triethylsilyl)oxy)ethanamine (3.57 g, 11.11 mmol) in DCM (37.0 mL) was added 3,3,3-trifluoro-2,2-dimethylpropanal (11.11 mmol) in DCM followed by AcOH (0.770 ml, 13.33 mmol) and NaBH(OAc)3 (3.53 g, 16.67 mmol). The yellow heterogeneous mixture was stirred at room temperature. After 8 h, the mixture was quenched with saturated NaHCO3 (100 mL). The reaction mixture was extracted with DCM (2×100 mL). The organic extract was dried over Na2SO4. The solution was filtered and concentrated in vacuo to give the crude material as orange syrup. The crude material was absorbed onto a plug of silica gel and purified by silica gel column chromatography eluting with a gradient of 0% to 20% EtOAc in heptane to provide N-(2-(3,5-dichloropyridin-4-yl)-2-((triethylsilyl)oxy)ethyl)-3,3,3-trifluoro-2,2-dim ethylpropan-1-amine (A294) (3.4393 g, 7.72 mmol, 69.5% yield) as colorless oil. 1H NMR (400 MHz, CDCl3) δ 8.44 (2H, s), 5.48 (1H, dd, J=7.7, 4.4 Hz), 3.27 (1H, dd, J=12.3, 8.4 Hz), 2.58-2.83 (3H, m), 1.25-1.44 (1H, m), 1.10 (6H, s), 0.85-0.94 (9H, m), 0.47-0.64 (6H, m); LCMS (ESI) m/z 445.1 (M+H)+.

Workup

  1. customthe mixture was quenched with saturated NaHCO3 (100 mL)
  2. extractionThe reaction mixture was extracted with DCM (2×100 mL)
  3. extractionThe organic extract
  4. dry with materialwas dried over Na2SO4
  5. filtrationThe solution was filtered
  6. concentrationconcentrated in vacuo
  7. customto give the crude material as orange syrup
  8. customThe crude material was absorbed onto a plug of silica gel
  9. custompurified by silica gel column chromatography
  10. washeluting with a gradient of 0% to 20% EtOAc in heptane

Sources & evidence

ORD record
ord-38faa3c95e24417d9207daaff847adfc
Source dataset
uspto-grants-2016_06
Patent number
US09365522B2

Reaction notes

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