4-Cyanobenzaldehyde → HCID 123820452, compound

HRID 717077Notes

Reaction equation

HRID 717077 reaction equation
[CH:1]([C:3]1[CH:10]=[CH:9][C:6]([C:7]#[N:8])=[CH:5][CH:4]=1)=O.Cl.[C:12]([Si:16]([C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)([C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[O:17][C:18]1([CH3:22])[CH2:21][NH:20][CH2:19]1)([CH3:15])([CH3:14])[CH3:13].CO.CN(C=O)C.C([BH3-])#N.[Na+]>C(O)(=O)C>[C:12]([Si:16]([C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1)([C:29]1[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=1)[O:17][C:18]1([CH3:22])[CH2:19][N:20]([CH2:1][C:3]2[CH:10]=[CH:9][C:6]([C:7]#[N:8])=[CH:5][CH:4]=2)[CH2:21]1)([CH3:13])([CH3:14])[CH3:15]

Participants

6

Reactant 4

HCID 660424-CyanobenzaldehydeHCID 5003444Sodium cyanoborohydrideHCID 21901440N,N-dimethylformamide methanolHCID 131734155HCID 131734155, compound

Product 1

HCID 123820452HCID 123820452, compoundYield 87.2%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of 4-formylbenzonitrile (68 mg, 0.51 mmol) and 3-(tert-Butyl-diphenyl-silanyloxy)-3-methyl-azetidine hydrochloride (188 mg, 0.51 mmol) in 1:1 MeOH/DMF (26 mL) was added acetic acid (catalytic). The reaction mixture was stirred under N2 at 0° C. for 1 h. Sodium cyanoborohydride (1M in THF, 0.6 mL, 0.57 mmol) was added and the reaction mixture stirred at RT, under N2 for 18 h. The reaction mixture was concentrated in vacuo, the residue suspended in H2O (10 mL), washed with CH2Cl2 (2×10 mL) and the solution passed through a phase separation cartridge. The combined organic layers were concentrated in vacuo and the crude residue purified by silica gel chromatography eluting with 100% isohexane and increasing the polarity 100% EtOAc to afford 4-[3-(tert-butyl-diphenyl-silanyloxy)-3-methyl-azetidin-1-ylmethyl]-benzonitrile as a colourless oil (196 mg, 86%).

Workup

  1. stirringthe reaction mixture stirred at RT, under N2 for 18 h
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. washwashed with CH2Cl2 (2×10 mL)
  4. customthe solution passed through a phase separation cartridge
  5. concentrationThe combined organic layers were concentrated in vacuo
  6. customthe crude residue purified by silica gel chromatography
  7. washeluting with 100% isohexane
  8. temperatureincreasing the polarity 100% EtOAc

Sources & evidence

ORD record
ord-12781841910b462dba066ba7975c83f4
Source dataset
uspto-grants-2015_11
Patent number
US09193689B2

Reaction notes

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