Water → [5'-(Aminomethyl)-2'-fluoro-3-biphenylyl]methanol

HRID 662018Notes

Reaction equation

HRID 662018 reaction equation
[OH:1][CH2:2][C:3]1[CH:4]=[C:5](B(O)O)[CH:6]=[CH:7][CH:8]=1.Cl.Br[C:14]1[CH:15]=[C:16]([CH2:21][NH2:22])[CH:17]=[CH:18][C:19]=1[F:20].C(=O)([O-])[O-].[K+].[K+].O>O1CCOCC1.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[NH2:22][CH2:21][C:16]1[CH:15]=[CH:14][C:19]([F:20])=[C:18]([C:5]2[CH:6]=[CH:7][CH:8]=[C:3]([CH2:2][OH:1])[CH:4]=2)[CH:17]=1

Participants

7

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 27249011-(3-Bromo-4-fluorophenyl)methanamine hydrochlorideHCID 2734662[3-(Hydroxymethyl)phenyl]boronic acid

Product 1

HCID 57813296[5'-(Aminomethyl)-2'-fluoro-3-biphenylyl]methanolYield 13.2%

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
150 °C

Procedure

To a solution of [3-(hydroxymethyl)phenyl]boronic acid (2 g, 13.2 mmol) in 1,4-dioxan (40 mL) was added [(3-bromo-4-fluorophenyl)methyl]amine hydrochloride (3.18 g, 13.2 mmol), potassium carbonate (9.1 g, 66 mmol) and tetrakis(triphenylphosphine) palladium(0) (456 mg, 0.4 mmol). The mixture was split into 4×20 mL capacity microwave vials and each was treated with water (3 mL). The mixtures were each heated at 150° C. for 20 mins. One sixth of the total reaction mixture was treated with water (100 mL) and extracted with ethyl acetate (2×80 mL). The combined organic phase was dried (magnesium sulphate) and evaporated to dryness and the product purified by flash chomatography on silica using 0-50% ethyl acetate/cyclohexane followed by dichloromethane/ammonia solution/methanol @8:1:1 as eluants. Product-containing fractions were combined and evaporated to dryness to afford 402 mg of the title compound. LC-MS m/z 463 (M+H)+, 0.65 min (ret time). The remaining five-sixths of the reaction mixture was worked up in the same manner and purified by flash chomatography using ethyl acetate/cyclohexane @1:1 followed by dichloromethane/ammonia solution/methanol @8:1:1 as eluants. This yielded 1.97 g of the title compound. LC-MS m/z 463 (M+H)+, 0.65 min (ret time).

Workup

  1. customThe mixture was split into 4×20 mL capacity microwave vials
  2. additioneach was treated with water (3 mL)
  3. customOne sixth of the total reaction mixture
  4. extractionextracted with ethyl acetate (2×80 mL)
  5. dry with materialThe combined organic phase was dried (magnesium sulphate)
  6. customevaporated to dryness
  7. customthe product purified by flash chomatography on silica using 0-50% ethyl acetate/cyclohexane
  8. customevaporated to dryness

Sources & evidence

ORD record
ord-911c812d0e274880aed5313b1727bc04
Source dataset
uspto-grants-2011_12
Patent number
US08084449B2

Reaction notes

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