Acetic Acid → HCID 123150186, compound

HRID 2202692Notes

Reaction equation

HRID 2202692 reaction equation
[Cl:1][C:2]1[CH:3]=[N:4][C:5]2[C:10]([C:11]=1[CH:12]([O:15][Si:16]([CH2:21][CH3:22])([CH2:19][CH3:20])[CH2:17][CH3:18])[CH2:13][NH2:14])=[CH:9][CH:8]=[CH:7][CH:6]=2.[CH3:23][C:24]([CH3:28])([CH3:27])[CH:25]=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][C:5]2[C:10]([C:11]=1[CH:12]([O:15][Si:16]([CH2:19][CH3:20])([CH2:17][CH3:18])[CH2:21][CH3:22])[CH2:13][NH:14][CH2:23][C:24]([CH3:28])([CH3:27])[CH3:25])=[CH:9][CH:8]=[CH:7][CH:6]=2

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 12417PivalaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 123552372HCID 123552372, compound

Product 1

HCID 123150186HCID 123150186, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a yellow clear solution of 2-(3-chloroquinolin-4-yl)-2-((triethylsilyl)oxy)ethanamine (A275-6) (0.217 g, 0.644 mmol) in DCM (2.15 mL) was added trimethylacetaldehyde (0.077 mL, 0.71 mmol), AcOH (0.045 mL, 0.77 mmol), and NaBH(OAc)3 (0.205 g, 0.966 mmol). The yellow homogeneous mixture was stirred at room temperature. After 2 h, the mixture was quenched with water (20 mL) and neutralized with 0.5 M NaOH (10 mL) to pH ˜9.0. The reaction mixture was extracted with DCM (2×50 mL). The organic extract washed with saturated NaCl (1×50 mL) and dried over Na2SO4. The solution was filtered and concentrated in vacuo to give the crude material as a yellow syrup. The crude material was absorbed onto a plug of silica gel and purified by chromatography through a REDISEP™ pre-packed silica gel column (40 g), eluting with a gradient of 0% to 20% EtOAc in hexane, and dried under high vacuum to give N-(2-(3-chloroquinolin-4-yl)-2-((triethylsilyl)oxy)ethyl)-2,2-dimethylpropan-1-amine (A275) as colorless syrup. 1H NMR (400 MHz, DMSO-d6) δ 8.84 (1H, s), 8.75 (1H, d, J=7.2 Hz), 8.04 (1H, dd, J=8.4, 1.0 Hz), 7.77 (1H, ddd, J=8.4, 6.9, 1.4 Hz), 7.61-7.68 (1H, m), 5.70 (1H, dd, J=7.7, 5.0 Hz), 3.26 (1H, dd, J=12.6, 8.1 Hz), 2.85 (1H, dd, J=12.6, 5.0 Hz), 2.23-2.39 (2H, m), 1.72 (1H, br. s.), 0.81 (9H, s), 0.72-0.79 (9H, m), 0.36-0.56 (6H, m); LCMS (ESI) m/z 407.1 (M+H)+.

Workup

  1. customthe mixture was quenched with water (20 mL)
  2. extractionThe reaction mixture was extracted with DCM (2×50 mL)
  3. extractionThe organic extract
  4. washwashed with saturated NaCl (1×50 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationThe solution was filtered
  7. concentrationconcentrated in vacuo
  8. customto give the crude material as a yellow syrup
  9. customThe crude material was absorbed onto a plug of silica gel
  10. custompurified by chromatography through a REDISEP™ pre-packed silica gel column (40 g)
  11. washeluting with a gradient of 0% to 20% EtOAc in hexane
  12. customdried under high vacuum

Sources & evidence

ORD record
ord-cda50875ac8c461fa135ac5503615317
Source dataset
uspto-grants-2016_06
Patent number
US09365522B2

Reaction notes

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