Hydrochloric Acid → HCID 23288959、化合物

HRID 368736

反応式

HRID 368736 の反応式
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([CH2:10][C:11]#[N:12])=[CH:2]1.[H-].[Na+].Br[CH2:16][CH2:17][CH2:18][O:19]C(=O)C.Cl.[OH-:24].[K+]>CN(C=O)C.[Cl-].[Na+].O.O.CCOC(C)=O>[OH:19][CH:18]([N:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([CH2:10][C:11]([NH2:12])=[O:24])=[CH:2]1)[CH2:17][CH3:16]

参加物

10

反応物 5

HCID 313Hydrochloric Acid2 回HCID 14797Potassium HydroxideHCID 24758Sodium hydrideHCID 351795Indole-3-acetonitrileHCID 122357751-Propanol, 3-bromo-, 1-acetate

生成物 1

HCID 23288959HCID 23288959、化合物収率 61.2%

試薬・触媒・溶媒 4

HCID 962Water溶媒2 回HCID 6228Dimethylformamide溶媒3 回HCID 8857Ethyl Acetate溶媒2 回HCID 57417360Sodium chloride; water溶媒2 回

実験手順

A solution of 3-indolylacetonitrile (3.00 g, 19.2 mmol) in DMF (30 mL) was added dropwise to a suspension of sodium hydride (1.08 g, 27.0 mmol) in DMF (10 mL) at room temperature. The resultant mixture was stirred at room temperature for 30 min. before a solution of 3-bromopropylacetate (4.87 g, 26.9 mmol) in DMF (15 mL) was added. The reaction was stirred an additional 3 hours at room temperature before being worked up extractively with EtOAc (250 mL), aqueous 0.5N HCl (200 mL), water (200 mL) and brine (50 mL) and the solvent was removed in vacuo to give 6.91 g (>100%) of crude alkylated product which was converted to 1-(1-hydroxypropyl)-indole-3-acetamide without purification as follows. The oil was dissolved in tert-butanol (70 mL), treated with freshly powdered potassium hydroxide (85%, 12.7 g, 192 mmol) and the resultant mixture heated to a gentle reflux for 1 hr. The reaction mixture was then poured into ice and the acidity adjusted to pH~1 using aqueous 6N HCl (35 mL). The reaction was worked up extractively using EtOAc (300 mL), water (200 mL), brine (50 ml) and the organic layer dried (MgSO4) and the solvent removed in vacuo to give a solid that was purified by flash chromatography using a 2:1 acetone:hexanes initially followed by 95:5 acetone:MeOH to give 2.73 g (61%) of 1-(1-Hydroxypropyl)-indole-3-acetamide. NMR. MS (FD) m/z=232 (M+, 100%). Analytical calculated for C13H16N2O2C, 67.22; H, 6.94; N, 12.06. Found C, 65.99; H, 7.24; N, 11.0.

後処理

  1. additionwas added
  2. customthe solvent was removed in vacuo
  3. customto give 6.91 g (>100%) of crude alkylated product which
  4. customwas converted to 1-(1-hydroxypropyl)-indole-3-acetamide without purification
  5. dissolutionThe oil was dissolved in tert-butanol (70 mL)
  6. temperaturea gentle reflux for 1 hr
  7. additionThe reaction mixture was then poured into ice
  8. dry with materialthe organic layer dried (MgSO4)
  9. customthe solvent removed in vacuo
  10. customto give a solid
  11. customthat was purified by flash chromatography

出典と根拠

ORDレコード
ord-6acd4fdb5b2041efaf2487c716d43941
出典データセット
uspto-grants-2000_10
特許番号
US06133452

関連ノート

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