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

HRID 1096766Notes

Reaction equation

HRID 1096766 reaction equation
[C:1]1([C@:11]23[CH2:16][C@H:15]2[CH2:14][C:13](=O)[CH2:12]3)[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.C([O-])(=O)C.[NH4+].C([BH3-])#[N:24].[Na+].C(OCC)(=O)C.CO.C(N(CC)CC)C>CO>[C:1]1([C@:11]23[CH2:16][C@H:15]2[CH2:14][CH:13]([NH2:24])[CH2:12]3)[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1

Participants

6

Reactant 4

HCID 517165Ammonium AcetateHCID 5003444Sodium cyanoborohydrideHCID 21980445Ethyl acetate methanol triethylamineHCID 66781229(1S,5S)-1-(1-naphthyl)bicyclo[3.1.0]hexan-3-one

Product 1

HCID 59779166(1S,5S)-1-(1-naphthyl)bicyclo[3.1.0]hexan-3-amineYield 346.7%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of (1S,5S)-1-(1-naphthyl)bicyclo[3.1.0]hexan-3-one (0.7 g, 3.1 mmol) in methanol (87.5 mL) was added ammonium acetate (24.3 g, 310 mmol), stirred for 15 minutes at room temperature and sodium cyanoborohydride (1.58 g, 25 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 (50 mL). The aqueous layer was extracted with ethyl acetate (3×150 mL). The aqueous layer was saturated with sodium chloride and re-extracted with ethyl acetate (3×150 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 400 mg (57%) of 99% pure product. 1H NMR δ(300 MHz,CD3OD): 1.1-1.15 (1H,m), 1.21-1.24 (1H,m), 1.88-1.93 (2H,m), 2.24-2.31 (1H,m), 2.45-2.57 (1H,m), 2.90-2.92 (1H,m), 4.10-4.2 (1H,m), 7.37-7.57 (4H,m), 7.74-7.76 (1H,d, 6 Hz), 7.85-7.88 (1H,d,9 Hz), 8.20-8.29 (1H,m). 13CNMR (CD3OD): 140.74, 140.30, 135.51, 133.93, 129.81, 128.64, 127.76, 127.12, 127.01, 126.74, 126.59, 125.67 119.93, 54.97, 43.08, 40.42, 36.16, 34.53, 33.91, 25.88, 24.94, 23.70, 15.76. Purity: 98.5% (a/a) by HPLC. MS, M+(224).

Workup

  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 (50 mL)
  5. extractionThe aqueous layer was extracted with ethyl acetate (3×150 mL)
  6. extractionre-extracted with ethyl acetate (3×150 mL)
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-9720f062fffe4ae8a6563e2530661228
Source dataset
uspto-grants-2012_03
Patent number
US08138377B2

Reaction notes

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