Acetic Acid → 2-Methyl-2-[({6-[3-(trimethylsilyl)phenyl]pyridin-2-yl}methyl)amino]propan-1-ol

HRID 1472917Notes

Reaction equation

HRID 1472917 reaction equation
[CH3:1][Si:2]([CH3:18])([CH3:17])[C:3]1[CH:4]=[C:5]([C:9]2[N:14]=[C:13]([CH:15]=O)[CH:12]=[CH:11][CH:10]=2)[CH:6]=[CH:7][CH:8]=1.[NH2:19][C:20]([CH3:24])([CH3:23])[CH2:21][OH:22].C(O)(=O)C.C([BH3-])#N>CO>[CH3:23][C:20]([NH:19][CH2:15][C:13]1[CH:12]=[CH:11][CH:10]=[C:9]([C:5]2[CH:6]=[CH:7][CH:8]=[C:3]([Si:2]([CH3:18])([CH3:17])[CH3:1])[CH:4]=2)[N:14]=1)([CH3:24])[CH2:21][OH:22]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 118072-Amino-2-methyl-1-propanolHCID 498716Cyano-borohydrideHCID 247300856-(3-(Trimethylsilyl)phenyl)picolinaldehyde

Product 1

HCID 683126252-Methyl-2-[({6-[3-(trimethylsilyl)phenyl]pyridin-2-yl}methyl)amino]propan-1-olYield 54.4%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of Example 226A (1.00 g, 3.92 mmol) in methanol (20 mL) at ambient temperature was added 2-amino-2-methyl-1-propanol (0.349 g, 3.92 mmol), acetic acid (0.90 mL, 15.7 mmol) followed by MP-cyanoborohydride (2.49 mmol/g; 1.5 g). After 2 hours, the mixture was filtered, concentrated and the residue partitioned between ether and 1N NaOH. The organic layer was extracted with 1N aquoues HCl (×2) and the organic phase discarded. The aqueous layer was neutralized with 1N NaOH and extracted with EtOAc. The EtOAc extract was dried and concentrated to provide 700 mg (54%) of the title compound. MS (DCI+) m/z 329 (M+H); 1H NMR (300 MHz, CDCl3) δ 8.10 (s, 1H), 7.97-7.90 (m, 1H), 7.73 (t, J=7.7 Hz, 1H), 7.64-7.54 (m, 2H), 7.48 (t, J=7.5 Hz, 1H), 7.22 (d, J=7.7 Hz, 1H), 3.95 (s, 2H), 3.42 (s, 2H), 1.18 (s, 6H), 0.39-0.25 (m, 9H).

Workup

  1. filtrationthe mixture was filtered
  2. concentrationconcentrated
  3. customthe residue partitioned between ether and 1N NaOH
  4. extractionThe organic layer was extracted with 1N aquoues HCl (×2)
  5. extractionextracted with EtOAc
  6. extractionThe EtOAc extract
  7. customwas dried
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-4b6bb051f0f940ae9026652a383735e1
Source dataset
uspto-grants-2015_04
Patent number
US09012651B2

Reaction notes

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