Acetic Acid → (R)-4-[(1-Methyl-2,2,2-trifluoro-ethylamino)-methyl]-benzonitrile

HRID 1191006ノート

反応式

HRID 1191006 の反応式
C([BH3-])#N.[Na+].[C:5]([C:7]1[CH:14]=[CH:13][C:10]([CH:11]=O)=[CH:9][CH:8]=1)#[N:6].Cl.[CH3:16][C@@H:17]([NH2:22])[C:18]([F:21])([F:20])[F:19].C(O)(=O)C>CO>[CH3:16][C@@H:17]([NH:22][CH2:11][C:10]1[CH:13]=[CH:14][C:7]([C:5]#[N:6])=[CH:8][CH:9]=1)[C:18]([F:21])([F:20])[F:19]

参加物

6

反応物 4

HCID 176Acetic AcidHCID 660424-CyanobenzaldehydeHCID 5003444Sodium cyanoborohydrideHCID 44593757(R)-2-Amino-1,1,1-trifluoropropane hydrochloride

生成物 1

HCID 59828823(R)-4-[(1-Methyl-2,2,2-trifluoro-ethylamino)-methyl]-benzonitrile収率 27.2%

試薬・触媒・溶媒 1

HCID 887Methanol溶媒

実験手順

Add sodium cyanoborohydride (3.36 g, 53.5 mmol) to a solution of 4-cyanobenzaldehyde (1.75 g, 13.35 mmol) and (R)-1-methyl-2,2,2-trifluoro-ethylamine hydrochloride (2 g, 13.37 mmol) in methanol (17 mL) containing acetic acid (1.53 mL, 26.75 mmol). Stir the mixture at room temperature overnight. Partition the mixture between 1N aqueous NaOH/DCM (1:1, 500 mL) and extract the aqueous layer twice with DCM. Dry the combined organic extracts over MgSO4, concentrate in vacuo and purify by chromatography on silica gel (120 g) eluting with hexane/EtOAc (19:1, 9:1, 85:15 and 4:1) to obtain the desired intermediate (0.83 g, 27%). MS (ES+) m/z: 229 (M+H)+.

後処理

  1. customPartition the mixture between 1N aqueous NaOH/DCM (1:1, 500 mL)
  2. extractionextract the aqueous layer twice with DCM
  3. dry with materialDry the combined organic extracts over MgSO4
  4. concentrationconcentrate in vacuo
  5. custompurify by chromatography on silica gel (120 g)
  6. washeluting with hexane/EtOAc (19:1, 9:1, 85:15 and 4:1)

出典と根拠

ORDレコード
ord-e6d71cbd1e324fadb2d0c77c10a71133
出典データセット
uspto-grants-2014_03
特許番号
US08680091B2

反応ノート

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