2-Chloropyrimidine → 2-[3-(4-Pyrrolidin-1-ylmethyl-phenyl)-cyclobutylmethoxy]-pyrimidine

HRID 1241509Notes

Reaction equation

HRID 1241509 reaction equation
[N:1]1([CH2:6][C:7]2[CH:12]=[CH:11][C:10]([CH:13]3[CH2:16][CH:15]([CH2:17][OH:18])[CH2:14]3)=[CH:9][CH:8]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.Cl[C:20]1[N:25]=[CH:24][CH:23]=[CH:22][N:21]=1>C1COCC1>[N:1]1([CH2:6][C:7]2[CH:12]=[CH:11][C:10]([CH:13]3[CH2:14][CH:15]([CH2:17][O:18][C:20]4[N:25]=[CH:24][CH:23]=[CH:22][N:21]=4)[CH2:16]3)=[CH:9][CH:8]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

4

Reactant 2

HCID 744042-ChloropyrimidineHCID 21934866[3-(4-Pyrrolidin-1-ylmethyl-phenyl)-cyclobutyl]-methanol

Product 1

HCID 219348452-[3-(4-Pyrrolidin-1-ylmethyl-phenyl)-cyclobutylmethoxy]-pyrimidine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirring solution of [3-(4-pyrrolidin-1-ylmethyl-phenyl)-cyclobutyl]-methanol (38.0 mg, 0.16 mmol) prepared above (Step F) in 1.5 mL of THF was added 2-chloropyrimidine (21.3 mg, 0.19 mmol) followed by a solution of KotBu (310 uL, 0.31 mmol, 1 M THF). The reaction immediately turned to a dark pink/milky solution. When mass spectral analysis indicated complete consumption of starting alcohol (15 minutes) the reaction was quenched with an aqueous solution of NH4Cl. The reaction was diluted with a 3:1 mixture of chloroform/isopropyl alcohol. The layers were separated and the organic layer was dried over MgSO4, filtered through a fritted glass filter, and concentrated under reduced pressure to yield the title compound as a mixture of cis:trans isomers. Conversion to the HCl salt was accomplished by dissolving the free base in EtOAc, and then adding 1 eq of a solution of HCl (1 M THF). The colorless solid was collected and dried under reduced pressure to yield 45 mg of a colorless solid, and as a mixture of isomers.

Workup

  1. customThe reaction
  2. customconsumption of starting alcohol (15 minutes) the reaction
  3. customwas quenched with an aqueous solution of NH4Cl
  4. additionThe reaction was diluted with a 3:1 mixture of chloroform/isopropyl alcohol
  5. customThe layers were separated
  6. dry with materialthe organic layer was dried over MgSO4
  7. filtrationfiltered through a fritted glass
  8. filtrationfilter
  9. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-d33f425f84ba485a8b9f057e37732892
Source dataset
uspto-grants-2006_10
Patent number
US07115600B2

Reaction notes

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