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

HRID 1096765Notes

Reaction equation

HRID 1096765 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 66781762(1R,5R)-1-(1-naphthyl)bicyclo[3.1.0]hexan-3-one

Product 1

HCID 59779151(1R,5R)-1-(1-naphthyl)bicyclo[3.1.0]hexan-3-amineYield 99%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of (1R,5R)-1-(1-naphthyl)bicyclo[3.1.0]hexan-3-one (480 mg, 2.1 mmol) in methanol (60 mL) was added ammonium acetate (16.8 g, 210 mmol), stirred for 15 min at room temperature and sodium cyanoborohydride (1.08 g, 17 mmol) 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 (25 mL) and the aqueous layer was extracted with ethyl acetate (3×100 mL). The aqueous layer was saturated with sodium chloride and re-extracted with ethyl acetate (3×100 mL). The organic layers were combined, dried over anhydrous sodium sulfate, filtered and evaporated under reduced pressure to yield 1.5 g of crude oil, which was purified by preparative HPLC to give 280 mg (58%) of 99% pure product. 1H NMR δ(300 MHz,CD3OD): 1.10-1.23 (2H,m), 1.86-1.98 (2H,m) 2.25-2.31 (1H,m), 2.44-2.51 (1H,m), 2.90 (1H,m), 4.06-4.08 (1H,m), 7.33-7.56 (4H,m), 7.71-7.74 (1H,d,6 Hz), 7.82-7.85 (1H, d, 9 Hz), 8.20-8.28 (1H, m). 13CNMR(CD3OD): 140.75, 140.30, 135.49, 135.44, 133.92, 129.78, 128.61, 127.75, 127.09, 127.00, 126.72, 126.67, 126.58, 126.52, 125.68, 54.95, 43.05, 40.40, 36.35, 34.52, 33.88, 33.64, 25.86, 24.94, 23.70, 15.70.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. customto remove methanol at 30° C.
  3. customthe crude mass was quenched with water (25 mL)
  4. extractionthe aqueous layer was extracted with ethyl acetate (3×100 mL)
  5. extractionre-extracted with ethyl acetate (3×100 mL)
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. customevaporated under reduced pressure
  9. customto yield 1.5 g of crude oil, which
  10. customwas purified by preparative HPLC

Sources & evidence

ORD record
ord-f2bc1c9c160e43b9aa64f4906f50426e
Source dataset
uspto-grants-2012_03
Patent number
US08138377B2

Reaction notes

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