Piperidine → (2R,3S)-3-(tert-butoxy)-2-((2-chloropyrimidin-4-yl)amino)butan-1-ol

HRID 57349Notes

Reaction equation

HRID 57349 reaction equation
C1C2C(OC(=O)[N:16]([CH3:27])[C@@H:17]([C@@H:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])[CH3:21])[CH2:18][OH:19])C3C(=CC=CC=3)C=2C=CC=1.N1CCCCC1.[Cl:35][C:36]1[N:41]=C(Cl)[CH:39]=[CH:38][N:37]=1.CCN(C(C)C)C(C)C>O.CCOC(C)=O.CCCCCCC.C(#N)C>[C:23]([O:22][C@@H:20]([CH3:21])[C@H:17]([NH:16][C:27]1[CH:39]=[CH:38][N:37]=[C:36]([Cl:35])[N:41]=1)[CH2:18][OH:19])([CH3:24])([CH3:25])[CH3:26]

Participants

8

Reactant 4

HCID 8082PiperidineHCID 775312,4-DichloropyrimidineHCID 81531DiisopropylethylamineHCID 131736953HCID 131736953, compound

Product 1

HCID 90417085(2R,3S)-3-(tert-butoxy)-2-((2-chloropyrimidin-4-yl)amino)butan-1-olYield 54%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 21899848Ethylacetate heptaneSolvent

Procedure

To a round bottom flask with stir bar was added (9H-fluoren-9-yl)methyl((2R,3S)-3-(tert-butoxy)-1-hydroxybutan-2-yl)carbamate (4.7 g, 12.3 mmol) and acetonitrile (100 mL) followed by the addition of piperidine (1.8 mL, 18.4 mmol). The flask was capped and stirred for 18 hr at room temperature. The volatiles were then removed. A white solid develops which contains the amino alcohol product and the fmoc deprotection by products. Solids were redissolved in acetonitrile (50 ml)(some of the fmoc polymer is insoluble) and 2,4-dichloropyrimidine (5.48 g, 36.8 mmol) and DIEA (2.141 mL, 12.26 mmol) were added. Resulting reaction mixture allowed to stir 18 hr at room temperature. The volatiles were again removed. Reaction mixture was diluted with water and extracted with EtOAc. Organic phases combined, washed with water, brine, dried (Na2SO4), filtered and concentrated onto silica gel. Silica gel column chromatography (EtOAc/Heptane 0 to 100%) provided (2R,3S)-3-(tert-butoxy)-2-((2-chloropyrimidin-4-yl)amino)butan-1-ol (1.80 g, 6.58 mmol, 54% yield) as a colorless oil which crystallizes upon standing. LCMS m/z 274.1 (M+H)+, Rt 0.56 min.

Workup

  1. customThe flask was capped
  2. stirringstirred for 18 hr at room temperature
  3. customThe volatiles were then removed
  4. dissolutionSolids were redissolved in acetonitrile (50 ml)(some of the fmoc polymer
  5. additionwere added
  6. customResulting
  7. customreaction mixture
  8. stirringto stir 18 hr at room temperature
  9. customThe volatiles were again removed
  10. customReaction mixture
  11. extractionextracted with EtOAc
  12. washwashed with water, brine
  13. dry with materialdried (Na2SO4)
  14. filtrationfiltered
  15. concentrationconcentrated onto silica gel

Sources & evidence

ORD record
ord-2ce5236097f5460dac098d6fcd8210f6
Source dataset
uspto-grants-2016_09
Patent number
US09434719B2

Reaction notes

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