Lithium Chloride → 5-(4-(benzyloxy)-3-fluorophenyl)-2-(cyclohexylmethyl)-3-methylpyrimidin-4(3H)-one

HRID 2241307Notes

Reaction equation

HRID 2241307 reaction equation
Br[C:2]1[C:3](=[O:16])[N:4]([CH3:15])[C:5]([CH2:8][CH:9]2[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]2)=[N:6][CH:7]=1.[CH2:17]([O:24][C:25]1[CH:30]=[CH:29][C:28](B(O)O)=[CH:27][C:26]=1[F:34])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.[Cl-].[Li+]>O1CCOCC1.C([O-])([O-])=O.[Na+].[Na+].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:17]([O:24][C:25]1[CH:30]=[CH:29][C:28]([C:2]2[C:3](=[O:16])[N:4]([CH3:15])[C:5]([CH2:8][CH:9]3[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]3)=[N:6][CH:7]=2)=[CH:27][C:26]=1[F:34])[C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1

Participants

7

Reactant 3

HCID 433294Lithium ChlorideHCID 27377884-Benzyloxy-3-fluorophenylboronic AcidHCID 685170185-bromo-2-(cyclohexylmethyl)-3-methylpyrimidin-4(3H)-one

Product 1

HCID 685158505-(4-(benzyloxy)-3-fluorophenyl)-2-(cyclohexylmethyl)-3-methylpyrimidin-4(3H)-one

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 10340Sodium CarbonateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A suspension of 5-bromo-2-(cyclohexylmethyl)-3-methylpyrimidin-4(3H)-one (0.047 g, 0.165 mmol), 4-(benzyloxy)-3-fluorophenylboronic acid (0.049 g, 0.198 mmol), Pd(PPh3)4 (0.009 g, 0.008 mmol) and lithium chloride (0.028 g, 0.659 mmol) in dioxane (1 mL) and 2 M aqueous Na2CO3 (1 mL) was stirred at 100° C. for 1 hour. The reaction mixture was cooled to room temperature and then partitioned between EtOAc and H2O. The layers were separated and the aqueous layer was re-extracted with EtOAc (1×). The combined organic layers were dried over Na2SO4, filtered and concentrated. The crude product was purified by flash column chromatography, eluting with 10:1 CH2Cl2/EtOAc. The product was obtained (0.048 g; 72%) as an off-white solid. LRMS (APCI pos) m/e 407 (M+1).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. custompartitioned between EtOAc and H2O
  3. customThe layers were separated
  4. extractionthe aqueous layer was re-extracted with EtOAc (1×)
  5. dry with materialThe combined organic layers were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude product was purified by flash column chromatography
  9. washeluting with 10:1 CH2Cl2/EtOAc
  10. customThe product was obtained (0.048 g; 72%) as an off-white solid

Sources & evidence

ORD record
ord-a5b1a8dd6c6348b2926074f7a5ff8172
Source dataset
uspto-grants-2010_05
Patent number
US07723330B2

Reaction notes

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