Formaldehyde → (cis)-2,6-Dimethyl-4-({1-[4-(trifluoromethyl)phenyl]-1H-tetrazol-5-yl}methyl)morpholine

HRID 517751Notes

Reaction equation

HRID 517751 reaction equation
[CH3:1][C@H:2]1[O:7][C@@H:6]([CH3:8])[CH2:5][NH:4][CH2:3]1.[CH2:9]=O.C[Si]([N:15]=[N+:16]=[N-:17])(C)C.[F:18][C:19]([F:29])([F:28])[C:20]1[CH:25]=[CH:24][C:23]([N+:26]#[C-:27])=[CH:22][CH:21]=1>CO>[CH3:8][C@H:6]1[O:7][C@@H:2]([CH3:1])[CH2:3][N:4]([CH2:9][C:27]2[N:26]([C:23]3[CH:22]=[CH:21][C:20]([C:19]([F:28])([F:29])[F:18])=[CH:25][CH:24]=3)[N:17]=[N:16][N:15]=2)[CH2:5]1

Participants

6

Reactant 4

HCID 712FormaldehydeHCID 78378AzidotrimethylsilaneHCID 6415002,6-Dimethylmorpholine, cis-HCID 27594124-(Trifluoromethyl)phenyl isocyanide

Product 1

HCID 56600738(cis)-2,6-Dimethyl-4-({1-[4-(trifluoromethyl)phenyl]-1H-tetrazol-5-yl}methyl)morpholineYield 78.5%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of (cis)-2,6-dimethylmorpholine (0.111 mL, 0.900 mmol, Alfa Aesar, Ward Hill, USA) and formaldehyde (37%, aqueous, 0.067 mL, 0.9 mmol) in methanol (4 mL) was stirred at room temperature for 1.5 h before adding trimethylsilyl azide (0.155 mL, 1.170 mmol) and 4-(trifluoromethyl)phenyl isocyanide (200 mg, 1.170 mmol). After stirring for 2 days at room temperature, the mixture was filtered and the solid collected was purified by silica gel column chromatography (Biotage SP4, gradient elution: 0-100% EtOAc in iso-hexane) to give the title compound as a solid (241 mg).

Workup

  1. filtrationthe mixture was filtered
  2. customthe solid collected
  3. customwas purified by silica gel column chromatography (Biotage SP4, gradient elution: 0-100% EtOAc in iso-hexane)

Sources & evidence

ORD record
ord-51e93fd5b263459c949304d7e932bc17
Source dataset
uspto-grants-2015_08
Patent number
US09115132B2

Reaction notes

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