Ammonium Acetate → (1S,5S)-1-(3,4-Dichlorophenyl)bicyclo[3.1.0]hexan-3-amine

HRID 1096764ノート

反応式

HRID 1096764 の反応式
[Cl:1][C:2]1[CH:3]=[C:4]([C@:9]23[CH2:14][C@H:13]2[CH2:12][C:11](=O)[CH2:10]3)[CH:5]=[CH:6][C:7]=1[Cl:8].C([O-])(=O)C.[NH4+].C([BH3-])#[N:22].[Na+].C(OCC)(=O)C.CO.C(N(CC)CC)C>CO>[Cl:1][C:2]1[CH:3]=[C:4]([C@:9]23[CH2:14][C@H:13]2[CH2:12][CH:11]([NH2:22])[CH2:10]3)[CH:5]=[CH:6][C:7]=1[Cl:8]

参加物

6

反応物 4

HCID 517165Ammonium AcetateHCID 5003444Sodium cyanoborohydrideHCID 21980445Ethyl acetate methanol triethylamineHCID 66781279(1S,5S)-1-(3,4-Dichlorophenyl)bicyclo[3.1.0]hexan-3-one

生成物 1

HCID 59779135(1S,5S)-1-(3,4-Dichlorophenyl)bicyclo[3.1.0]hexan-3-amine収率 99%

試薬・触媒・溶媒 1

HCID 887Methanol溶媒

実験手順

To a solution of (1S,5S)-1-(3,4-dichlorophenyl)bicyclo[3.1.0]hexan-3-one (0.7 g, 2.9 mmol) in methanol (87.5 mL) was added ammonium acetate (22.05 g, 290 mmol), stirred for 15 minutes at room temperature and sodium cyanoborohydride (1.45 g, 23 mmol) was added and the mixture was heated to 60° C. for 2 hours. The reaction was monitored by TLC (ethyl acetate/methanol/triethylamine (89:10:1)). The reaction mixture was concentrated under reduced pressure to remove methanol at 30° C., the crude mass was quenched with water (20 mL) and the aqueous layer was extracted with ethyl acetate (3×75 mL). The aqueous layer was saturated with sodium chloride and re-extracted with ethyl acetate (3×75 mL). The organic layers were combined, dried over anhydrous sodium sulfate, filtered and evaporated under reduced pressure to yield 2.4 g of crude oil, which was purified by preparative HPLC to yield 430 mg (66%) of 99% pure product. 1H NMR δ(300 MHz,CD3OD) 0.92-0.98 (2H,m), 1.28 (1H,m), 1.76-1.87 (3H,m), 2.08-2.14 (2H,m), 2.57-2.75 (3H,m), 3.98-4.04 (1H,m),7.10-7.15 (1H,m), 7.35-7.42 (2H,m). 13CNMR(CD3OD) δ: 145.91, 133.24, 131.51, 130.79, 129.78, 129.29, 127.58, 127.05, 54.33, 40.53, 37.67, 35.75, 34.36, 33.54, 31.10, 28.25, 26.08, 25.84, 18.53. Purity: 99.53% (a/a) by HPLC. MS, M+(241).

後処理

  1. temperaturethe mixture was heated to 60° C. for 2 hours
  2. concentrationThe reaction mixture was concentrated under reduced pressure
  3. customto remove methanol at 30° C.
  4. customthe crude mass was quenched with water (20 mL)
  5. extractionthe aqueous layer was extracted with ethyl acetate (3×75 mL)
  6. extractionre-extracted with ethyl acetate (3×75 mL)
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. customevaporated under reduced pressure
  10. customto yield 2.4 g of crude oil, which
  11. customwas purified by preparative HPLC

出典と根拠

ORDレコード
ord-d3d5eacc13d7409c8ecda5192604327b
出典データセット
uspto-grants-2012_03
特許番号
US08138377B2

反応ノート

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