(2R)-1-aminopropan-2-ol → HCID 11858494, compound

HRID 1815946Notes

Reaction equation

HRID 1815946 reaction equation
[NH2:1][CH2:2][C@H:3]([OH:5])[CH3:4].[CH2:6]([O:13][C:14]1[CH:21]=[CH:20][C:17]([C:18]#[N:19])=[C:16](F)[CH:15]=1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1>CS(C)=O>[CH2:6]([O:13][C:14]1[CH:15]=[CH:16][C:17]([C:18]#[N:19])=[C:20]([NH:1][CH2:2][C@H:3]([OH:5])[CH3:4])[CH:21]=1)[C:7]1[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=1

Participants

4

Reactant 2

HCID 439938(2R)-1-aminopropan-2-olHCID 113336284-(Benzyloxy)-2-fluorobenzonitrile

Product 1

HCID 11858494HCID 11858494, compound

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
125 °C

Procedure

A solution of (R)-(−)-1-amino-propan-2-ol (389 g, 5.19 mol) in dimethyl sulfoxide (600 mL) was added to a solution of the product from Step A (786 g, 3.46 mol), basic alumina (786 g), and 4 Å molecular sieves (131 g). The stirred mixture was heated at 110-140° C. for 24 h, cooled and filtered, the filter-aide was washed with 10 L of 4:1 ether-ethyl acetate followed by 4 L of 3:2 ethyl acetate-hexane. The organic washes were extracted with water (5 L) and the aqueous phase was extracted with 25% ethyl acetate-hexane (4×2 L). The combined organic phases were washed with water and brine, dried over sodium sulfate, concentrated to about 3 L and allowed to stand for 48 h. The precipitated solid was collected by filtration, washed with hexane, and vacuum-dried to provide the desired product in two crops (619 g and 86 g). The concentated supernatant was applied to a 5 kg silica gel pad and eluted with a gradient of 10-50% ethyl acetate-hexane to give, after concentration in vacuo, additional product (119 g): total yield was 791 g (81%).

Workup

  1. temperaturecooled
  2. filtrationfiltered
  3. washthe filter-aide was washed with 10 L of 4:1 ether-ethyl acetate
  4. extractionThe organic washes were extracted with water (5 L)
  5. extractionthe aqueous phase was extracted with 25% ethyl acetate-hexane (4×2 L)
  6. washThe combined organic phases were washed with water and brine
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated to about 3 L
  9. filtrationThe precipitated solid was collected by filtration
  10. washwashed with hexane
  11. customvacuum-dried

Sources & evidence

ORD record
ord-2dc3b9ab708549d8b7361e969c2d6e4f
Source dataset
uspto-grants-2005_04
Patent number
US06881749B2

Reaction notes

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