Citric Acid → N-[2-(1-aminopropyl)-5-(trifluoromethyl)benzyl]-N-[3,5-bis(trifluoromethyl)benzyl]-2-methyl-2H-tetrazol-5-amine

HRID 390746ノート

反応式

HRID 390746 の反応式
[F:1][C:2]([F:35])([F:34])[C:3]1[CH:4]=[C:5]([CH:27]=[C:28]([C:30]([F:33])([F:32])[F:31])[CH:29]=1)[CH2:6][N:7]([CH2:14][C:15]1[CH:22]=[C:21]([C:23]([F:26])([F:25])[F:24])[CH:20]=[CH:19][C:16]=1[C:17]#[N:18])[C:8]1[N:9]=[N:10][N:11]([CH3:13])[N:12]=1.[CH2:36]([Mg]Br)[CH3:37].[BH4-].[Na+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C1(C)C=CC=CC=1.CCOCC>[NH2:18][CH:17]([C:16]1[CH:19]=[CH:20][C:21]([C:23]([F:26])([F:25])[F:24])=[CH:22][C:15]=1[CH2:14][N:7]([CH2:6][C:5]1[CH:4]=[C:3]([C:2]([F:1])([F:34])[F:35])[CH:29]=[C:28]([C:30]([F:31])([F:32])[F:33])[CH:27]=1)[C:8]1[N:9]=[N:10][N:11]([CH3:13])[N:12]=1)[CH2:36][CH3:37]

参加物

7

反応物 4

HCID 311Citric AcidHCID 4311764Sodium borohydrideHCID 589664932-{[(3,5-bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amino]-methyl}-4-trifluoromethyl-benzonitrileHCID 178418443HCID 178418443、化合物

生成物 1

HCID 58966576N-[2-(1-aminopropyl)-5-(trifluoromethyl)benzyl]-N-[3,5-bis(trifluoromethyl)benzyl]-2-methyl-2H-tetrazol-5-amine収率 87%

試薬・触媒・溶媒 2

HCID 1140Toluene溶媒HCID 3283Diethyl Ether溶媒

実験手順

To a solution of 2-{[(3,5-bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amino]-methyl}-4-trifluoromethyl-benzonitrile (Preparation 7) (300.0 mg, 0.590 mmoles) in toluene (1.2 mL) was added ethyl magnesium bromide (0.59 mL, 1.77 mmoles of a 3M solution in ether) dropwise at room temperature and the reaction mixture was stirred for 2.5 hours. The reaction was quenched by adding methanol (0.98 mL) dropwise with stirring until methanol and toluene were thoroughly mixed. To this mixture sodium borohydride (22.3 mg, 0.590 mmoles) was added in one portion and the reaction stirred for 1.5 hours. A 10% aqueous citric acid (1.5 mL) solution was added drop wise at room temperature until bubbling stopped. The reaction mixture was made basic to pH 10 with 1 N NaOH solution. The organic layer was dried over sodium sulfate, filtered and concentrated. The crude product was purified using cation exchange resin (Waters Oasis MCX 6CC 500 mg LP Extraction Cartridge, Waters, Milford, Mass., USA) to yield the title compound (278.4 mg, 87% yield) as yellow gum. MS (ES+) Calc: 608.5, Found: 609.1 (M+1).

後処理

  1. customThe reaction was quenched
  2. additionby adding methanol (0.98 mL) dropwise
  3. stirringwith stirring until methanol and toluene
  4. additionwere thoroughly mixed
  5. stirringthe reaction stirred for 1.5 hours
  6. customuntil bubbling
  7. dry with materialThe organic layer was dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude product was purified
  11. extractioncation exchange resin (Waters Oasis MCX 6CC 500 mg LP Extraction Cartridge, Waters, Milford, Mass., USA)

出典と根拠

ORDレコード
ord-bc764583b40246de8ce12844c09e7934
出典データセット
uspto-grants-2013_02
特許番号
US08383660B2

反応ノート

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