Formaldehyde → (3R)-3-Methyl-4-({1-[4-(trifluoromethyl)phenyl]-1H-tetrazol-5-yl}methyl)morpholine hydrochloride

HRID 517764ノート

反応式

HRID 517764 の反応式
[ClH:1].[CH3:2][C@@H:3]1[CH2:8][O:7][CH2:6][CH2:5][NH:4]1.C([N:11]([CH2:14][CH3:15])[CH2:12][CH3:13])C.C=O.[F:18][C:19]([F:29])([F:28])[C:20]1[CH:25]=CC([N+]#[C-])=[CH:22][CH:21]=1.C[Si]([N:34]=[N+:35]=[N-:36])(C)C>CO>[ClH:1].[CH3:2][C@@H:3]1[CH2:8][O:7][CH2:6][CH2:5][N:4]1[CH2:15][C:14]1[N:11]([C:12]2[CH:13]=[CH:25][C:20]([C:19]([F:29])([F:28])[F:18])=[CH:21][CH:22]=2)[N:36]=[N:35][N:34]=1

参加物

7

反応物 5

HCID 712FormaldehydeHCID 8471TriethylamineHCID 78378AzidotrimethylsilaneHCID 27594124-(Trifluoromethyl)phenyl isocyanideHCID 57356922(3R)-3-Methylmorpholine hydrochloride

生成物 1

HCID 86691892(3R)-3-Methyl-4-({1-[4-(trifluoromethyl)phenyl]-1H-tetrazol-5-yl}methyl)morpholine hydrochloride収率 32.5%

試薬・触媒・溶媒 1

HCID 887Methanol溶媒

実験手順

To a solution of (3R)-3-methylmorpholine hydrochloride (122 mg, 0.887 mmol, Tyger Scientific, Ewing, USA) and triethylamine (0.124 mL, 0.887 mmol) in methanol (2 mL) was added formaldehyde (37% aqueous) (0.066 mL, 0.887 mmol). The reaction mixture was stirred at room temperature for 2 hours before the addition of 4-(trifluoromethyl)phenyl isocyanide (152 mg, 0.887 mmol) and trimethylsilylazide (0.118 mL, 0.887 mmol). The reaction mixture was stirred at room temperature overnight (approximately 18 hours) and the solvent removed under vacuum. The residue was purified by MDAP. Fractions containing the desired compound were combined and the solvent removed. The residue was partitioned between saturated NaHCO3 (2 mL) and DCM (5 ml). The organic layer was collected via a hydrophobic frit and the solvent removed under a stream of argon. The compound was dissolved in a minimum of diethyl ether before the addition of 1N HCl in diethyl ether (2 mL) leading to precipitation. The ether was decanted and the precipitate dried under vacuum to yield the title compound as a pale yellow solid (105 mg).

後処理

  1. customthe solvent removed under vacuum
  2. customThe residue was purified by MDAP
  3. additionFractions containing the desired compound
  4. customthe solvent removed
  5. customThe residue was partitioned between saturated NaHCO3 (2 mL) and DCM (5 ml)
  6. customThe organic layer was collected via a hydrophobic frit
  7. customthe solvent removed under a stream of argon
  8. dissolutionThe compound was dissolved in a minimum of diethyl ether before the addition of 1N HCl in diethyl ether (2 mL)
  9. customleading to precipitation
  10. customThe ether was decanted
  11. customthe precipitate dried under vacuum

出典と根拠

ORDレコード
ord-b023baf8508c49438a52f818e2523bee
出典データセット
uspto-grants-2015_08
特許番号
US09115132B2

反応ノート

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