Aluminium lithium hydride → HCID 54754812, compound

HRID 2406873Notes

Reaction equation

HRID 2406873 reaction equation
[CH3:1][C:2]12[C:11]([CH3:13])([CH3:12])[CH:8]([CH2:9][CH2:10]1)[C:4]1([CH2:7][CH2:6][CH2:5]1)[CH:3]2[NH:14][CH:15]=O.[H-].[Al+3].[Li+].[H-].[H-].[H-]>C1COCC1>[CH3:15][NH:14][C@@H:3]1[C:4]2([CH2:5][CH2:6][CH2:7]2)[C@@H:8]2[C:11]([CH3:13])([CH3:12])[C@@:2]1([CH3:1])[CH2:10][CH2:9]2

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 86691658HCID 86691658, compound

Product 1

HCID 54754812HCID 54754812, compoundYield 35%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of N-(4,7,7-trimethylspiro[bicyclo[2.2.1]heptane-2,1′-cyclobutan]-3-yl)formamide (1.50 g, 6.78 mmol) in THF (40 mL) at 0° C. was slowly added lithium aluminum hydride (27.1 mmol, 27.1 mL of 1.0 M solution in THF). After complete addition, the reaction was refluxed for 48 h. The reaction mixture was cooled to 0° C. and quenched by addition, in portions, of solid sodium sulfate decahydrate (10 g). After stirring for 1 h, this mixture was filtered, and the filtrate was concentrated. The residue was purified on a 40 g silica gel column, using 0-100% CMA (chloroform:methanol:30% aqueous ammonia; 9:1:0.1) in chloroform as the eluent, to obtain an exo amine product, (1S,3R,4R)—N,4,7,7-tetramethylspiro[bicyclo[2.2.1]heptane-2.1′-cyclobutan]-3-amine (0.49 g; 35% yield), and an endo-amine product, (1S,3S,4R)—N,4,7,7-tetramethylspiro[bicyclo[2.2.1]heptane-2,1′-cyclobutan]-3-amine (0.30 g; 21% yield), both as oils. The two products were converted to their hydrochloride salts by dissolving each in 1 mL of concentrated hydrochloric acid and concentrating and vacuum drying the samples. 1H NMR of exo-(1S,3R,4R)—N,4,7,7-tetramethylspiro[bicyclo[2.2.1]heptane-2,1′-cyclobutan]-3-amine hydrochloride (D2O 400 MHz): δ 2.80 (s, 3H), 2.72 (brs, 1H), 2.22-1.91 (m, 4H), 1.84-1.72 (m, 3H), 1.54-1.45 (m, 2H), 1.38-1.31 (m, 1H), 1.10-1.01 (m, 1H), 0.87 (s, 3H), 075 (s, 3H), 0.72 (s. 3H); LCMS (m/z): 208 (M+1). 1H NMR of endo-(1S,3S,4R)—N4,7,7-tetramethylspiro[bicyclo[2.2.1]heptane-2,1′-cyclobutan]-3-amine hydrochloride (D2O, 400 MHz); δ 3.12 (brs, 1H), 2.79 (s, 3H), 2.26-2.16 (m, 1H), 2.01-1.85 (m, 3H), 1.78-1.69 (m, 3H), 1.60-1.51 (m, 1H), 1.36-1.24 (m, 2H), 1.08-1.00 (m, 1H), 0.85 (s, 3H), 0.78 (s, 3H) 0.75 (s, 3H); LCMS (m/z): 208 (M+1).

Workup

  1. customat 0° C.
  2. additionAfter complete addition
  3. temperaturethe reaction was refluxed for 48 h
  4. customquenched by addition, in portions, of solid sodium sulfate decahydrate (10 g)
  5. filtrationthis mixture was filtered
  6. concentrationthe filtrate was concentrated
  7. customThe residue was purified on a 40 g silica gel column

Sources & evidence

ORD record
ord-55ddfe49791b455a958082b14cc5a638
Source dataset
uspto-grants-2014_08
Patent number
US08809397B2

Reaction notes

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