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

HRID 1096764노트

반응식

HRID 1096764 반응식
[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]

참가 물질

6

반응물 4

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

생성물 1

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

시약·촉매·용매 1

HCID 887Methanol용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-d3d5eacc13d7409c8ecda5192604327b
출처 데이터셋
uspto-grants-2012_03
특허 번호
US08138377B2

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