Water → HCID 60137814, compound

HRID 423621Notes

Reaction equation

HRID 423621 reaction equation
Cl[C:2]1[N:7]=[CH:6][C:5]([F:8])=[CH:4][N:3]=1.[NH:9]1[CH2:14][CH2:13][CH:12]([CH2:15][OH:16])[CH2:11][CH2:10]1.C([O-])([O-])=O.[K+].[K+].O>CS(C)=O>[F:8][C:5]1[CH:4]=[N:3][C:2]([N:9]2[CH2:14][CH2:13][CH:12]([CH2:15][OH:16])[CH2:11][CH2:10]2)=[N:7][CH:6]=1

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 4207714-PiperidinemethanolHCID 5834662-Chloro-5-fluoropyrimidine

Product 1

HCID 60137814HCID 60137814, compoundYield 95.3%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
100 °C

Procedure

A solution of 2-chloro-5-fluoropyrimidine (1.1 g, 8.05 mmol) and 4-piperidinemethanol (1.14 g, 9.66 mmol) in DMSO (20 mL) was treated with K2CO3 (2.23 g, 16.10 mmol). The reaction mixture was heated at 100° C. overnight. The mixture was cooled to ambient temperature and poured into water and extracted with CH2Cl2 (60 mL×3). The organic extracts were combined and washed with brine, dried over Na2SO4, filtered, and the filtrate was concentrated to give crude product as a brown oil. The crude product was purified by chromatography on an ISCO silica gel column using 0 to 40% EtOAc/hexanes to give 1.62 g (95%) of [1-(5-fluoro-2-pyrimidinyl)-4-piperidinyl]methanol as a white solid upon standing. 1H NMR (400 MHz, CDCl3): δ 8.18 (s, 2H), 4.75-4.65 (m, 2H), 3.51 (d, 2H, J=6.1 Hz), 2.95-2.80 (m, 2H), 1.85-1.70 (m, 3H), 1.30-1.15 (m, 2H); LRMS (ESI), m/z 212 (M+H).

Workup

  1. temperatureThe mixture was cooled to ambient temperature
  2. extractionextracted with CH2Cl2 (60 mL×3)
  3. washwashed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationthe filtrate was concentrated
  7. customto give crude product as a brown oil
  8. customThe crude product was purified by chromatography on an ISCO silica gel column

Sources & evidence

ORD record
ord-8fedf9052d7e445f96a3d195088ee35b
Source dataset
uspto-grants-2012_01
Patent number
US08101634B2

Reaction notes

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