Water → 2-(2',3'-Difluoro-4'-octyloxyphenyl)-5-bromopyrimidine

HRID 1603292Notes

Reaction equation

HRID 1603292 reaction equation
[Br:1][C:2]1[CH:3]=[N:4][C:5](I)=[N:6][CH:7]=1.C(=O)([O-])[O-].[Na+].[Na+].[F:15][C:16]1[C:21]([F:22])=[C:20]([O:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH3:31])[CH:19]=[CH:18][C:17]=1B(O)O.O>COCCOC.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>[F:15][C:16]1[C:21]([F:22])=[C:20]([O:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH3:31])[CH:19]=[CH:18][C:17]=1[C:5]1[N:4]=[CH:3][C:2]([Br:1])=[CH:7][N:6]=1

Participants

7

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 70066515-Bromo-2-iodopyrimidineHCID 10850744(2,3-Difluoro-4-(octyloxy)phenyl)boronic acid

Product 1

HCID 232970432-(2',3'-Difluoro-4'-octyloxyphenyl)-5-bromopyrimidineYield 55.5%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent2×

Procedure

--To a degassed mixture of 5-bromo-2-iodopyrimidine 2 (4.0 g, 14.0 mmol), tetrakis(triphenylphosphine)palladium (323 mg, 0.28 mmol), DME (30 ml), and aqueous 2M sodium carbonate (50 ml) was added 2,3-difluoro-4-octyloxyphenylboronic acid 3 (4.42 g, 15.4 mmol) dropwise in DME (10 ml) under an atmosphere of nitrogen. The mixture was heated under reflux overnight; water was added to the mixture and the organic layer was separated. The aqueous layer was extracted with ethyl acetate (twice) and the combined organic solutions were washed with brine and dried (MgSO4). The solvent was removed in vacuo and the residue was purified by flash chromatography (5% to 10% ethyl acetate-light petroleum; the crude material was preloaded onto silica in dichloromethane) to give the phenylpyrimidine 4 (3.1 g, 55%) (from methanol), m.p. 74.6° C.; νmax /cm-1 (KBr) 2920, 2850, 1625, 1475, 1420, 1310 and 1090; δ 0.91(1H, t, Me), 1.2-1.55(10H, m), 1.85 (2H, quint. OCH2CH2), 4.11 (2H, t, OCH2), 6.82 (1H, ddd, 5'-H), 7.83 (1H, ddd, 6'-H) and 8.86 (2H, s, 4- and 6-H); m/z 288 (M+ -C8H16), 286 (M+ -C8H16), 178 and 155.

Workup

  1. temperatureThe mixture was heated
  2. temperatureunder reflux overnight
  3. customthe organic layer was separated
  4. extractionThe aqueous layer was extracted with ethyl acetate (twice) and the combined organic solutions
  5. washwere washed with brine
  6. dry with materialdried (MgSO4)
  7. customThe solvent was removed in vacuo
  8. customthe residue was purified by flash chromatography (5% to 10% ethyl acetate-light petroleum

Sources & evidence

ORD record
ord-56e1a5a79a4b4d31bb1dddf0f7857242
Source dataset
uspto-grants-1999_11
Patent number
US05986096

Reaction notes

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