Ammonium Acetate → HCID 59779168, compound

HRID 1096763Notes

Reaction equation

HRID 1096763 reaction equation
[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]

Participants

6

Reactant 4

HCID 517165Ammonium AcetateHCID 5003444Sodium cyanoborohydrideHCID 21980445Ethyl acetate methanol triethylamineHCID 66781214HCID 66781214, compound

Product 1

HCID 59779168HCID 59779168, compoundYield 99%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of (1R,5R)-1-(3,4-dichlorophenyl)bicyclo[3.1.0]hexan-3-one (0.9 g, 3.73 mmol) in methanol (112 mL) was added ammonium acetate (28.3 g, 373 mmol), stirred for 15 minutes at room temperature and sodiumcyano borohydride (1.87 g, 30.8 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 residual mass was quenched with water (50 mL) and the aqueous layer was extracted again 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 sulphate, filtered and evaporated under reduced pressure to yield 2.4 g of crude oil, which was purified by preparative HPLC to give 600 mg (66%) of 99% pure product. 1H NMR δ(300 MHz,CD3OD): 0.92-0.99 (2H,m), 1.27 (1H,m), 1.78-1.83 (3H,m), 2.04-2.15 (2H,m), 2.57-2.74 (3H,m), 3.98-4.01 (1H,m), 7.11-7.14 (1H,m), 7.36-7.41 (2H,m). 13CNMR(CD3OD) δ: 145.92, 133.22, 131.50, 130.76, 129.77, 129.30, 127.57, 127.06, 54.35, 40.52, 37.67, 35.74, 34.36, 33.53, 31.10, 28.25, 26.08, 25.87, 18.50. Purity: 99.15% (a/a) by HPLC. MS, M+(241).

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 residual mass was quenched with water (50 mL)
  5. extractionthe aqueous layer was extracted again with ethyl acetate (3×100 mL)
  6. extractionre-extracted with ethyl acetate (3×100 mL)
  7. dry with materialdried over anhydrous sodium sulphate
  8. filtrationfiltered
  9. customevaporated under reduced pressure
  10. customto yield 2.4 g of crude oil, which
  11. customwas purified by preparative HPLC

Sources & evidence

ORD record
ord-7b98d54fe3f04ca4ae9d5a16c9b9cfb5
Source dataset
uspto-grants-2012_03
Patent number
US08138377B2

Reaction notes

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