Dichloromethane → 4-(5-(2-Amino-6-methoxymethyl-pyridin-3-yl)isoxazol-3-ylmethyl)-phenol

HRID 78170Notes

Reaction equation

HRID 78170 reaction equation
C([O:8][C:9]1[CH:30]=[CH:29][C:12]([CH2:13][C:14]2[CH:18]=[C:17]([C:19]3[C:20]([NH2:28])=[N:21][C:22]([CH2:25][O:26][CH3:27])=[CH:23][CH:24]=3)[O:16][N:15]=2)=[CH:11][CH:10]=1)C1C=CC=CC=1.ClCCl.B(Br)(Br)Br>CO>[NH2:28][C:20]1[C:19]([C:17]2[O:16][N:15]=[C:14]([CH2:13][C:12]3[CH:29]=[CH:30][C:9]([OH:8])=[CH:10][CH:11]=3)[CH:18]=2)=[CH:24][CH:23]=[C:22]([CH2:25][O:26][CH3:27])[N:21]=1

Participants

5

Reactant 3

HCID 6344DichloromethaneHCID 25134Boron tribromideHCID 592554553-(3-(4-Benzyloxy-benzyl)-isoxazol-5-yl)-6-methoxymethyl-pyridin-2-ylamine

Product 1

HCID 592552174-(5-(2-Amino-6-methoxymethyl-pyridin-3-yl)isoxazol-3-ylmethyl)-phenolYield 20%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
0 °C

Procedure

To a mixture of 3-(3-(4-benzyloxy-benzyl)-isoxazol-5-yl)-6-methoxymethyl-pyridin-2-ylamine (30 mg, 0.075 mmol) described in Example 26 and dichloromethane (1 mL) was added boron tribromide (220 μL, 1 M dichloromethane solution, 0.22 mmol) at −78° C., which was stirred for 1 hour at 0° C. The reaction mixture was cooled to −78° C., methanol was added at the same temperature, and the excess boron tribromide was quenched. The reaction mixture was gradually allowed to room temperature, a sodium acetate aqueous solution was added to the reaction mixture at room temperature, which was neutralized, after which water was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride, and was concentrated under a reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:heptane=2:1) to obtain the title compound (4.6 mg, 20%).

Workup

  1. temperatureThe reaction mixture was cooled to −78° C.
  2. customthe excess boron tribromide was quenched
  3. customwas gradually allowed to room temperature
  4. additiona sodium acetate aqueous solution was added to the reaction mixture at room temperature
  5. additionafter which water was added
  6. extractionthe mixture was extracted with ethyl acetate
  7. washThe organic layer was washed with saturated aqueous sodium chloride
  8. concentrationwas concentrated under a reduced pressure
  9. customThe residue was purified by silica gel column chromatography (ethyl acetate:heptane=2:1)

Sources & evidence

ORD record
ord-d7ca87d1efd449d48262b9e5599ec4b4
Source dataset
uspto-grants-2014_09
Patent number
US08841327B2

Reaction notes

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