Dichloromethane → HCID 17985031, compound

HRID 2118077Notes

Reaction equation

HRID 2118077 reaction equation
[F:1][C:2]([F:33])([F:32])[C:3]([CH:18]=[N:19][C:20]1[CH:29]=[CH:28][C:27]([F:30])=[C:26]2[C:21]=1[CH:22]=[N:23][C:24]([CH3:31])=[N:25]2)([OH:17])[CH2:4][C:5](C1C=CC(Cl)=CC=1OC)([CH3:7])[CH3:6].B(Br)(Br)Br.[C:38]([O-:41])(O)=O.[Na+].Cl[CH2:44][Cl:45]>>[Cl:45][C:44]1[CH:6]=[CH:5][C:4]([CH:18]([C:3]([OH:17])([CH2:4][C:5]([CH3:7])=[CH2:6])[C:2]([F:33])([F:32])[F:1])[NH:19][C:20]2[CH:29]=[CH:28][C:27]([F:30])=[C:26]3[C:21]=2[CH:22]=[N:23][C:24]([CH3:31])=[N:25]3)=[C:3]([O:41][CH3:38])[CH:2]=1

Participants

5

Reactant 4

HCID 6344Dichloromethane2×HCID 25134Boron tribromideHCID 516892Sodium BicarbonateHCID 17985021HCID 17985021, compound

Product 1

HCID 17985031HCID 17985031, compoundYield 26%

Procedure

3.1 g (6.4 mmol) of (rac) 1,1,1,-trifluoro-4-(4-chloro-2-methoxyphenyl)-2-[(8-fluoro-2-methyl-quinazol-5-yl)iminomethyl]-4-methyl-pentan-2-ol is introduced into 50 ml of dichloromethane and 128 ml of a 1 M solution of boron tribromide in dichloromethane is added in drops at −75° C. It is allowed to reach −20° C. within 2.5 hours. Then, the reaction mixture is added to 300 ml of a saturated NaHCO3 solution, stirred for 15 more minutes, the phases are separated, the aqueous phase is extracted with dichloromethane, the combined organic phases are washed with saturated NaHCO3 solution and saturated NaCl solution and dried with sodium sulfate. After the solvent is removed in a rotary evaporator, the crude product is chromatographed on silica gel (eluant: hexane/ethyl acetate 3:1 to 1:1). Then, it is purified again by means of HPLC. 650 mg (26%) of the desired product is obtained as a yellow solid.

Workup

  1. additionis added in drops at −75° C
  2. customthe phases are separated
  3. extractionthe aqueous phase is extracted with dichloromethane
  4. washthe combined organic phases are washed with saturated NaHCO3 solution and saturated NaCl solution
  5. dry with materialdried with sodium sulfate
  6. customAfter the solvent is removed in a rotary evaporator
  7. customthe crude product is chromatographed on silica gel (eluant: hexane/ethyl acetate 3:1 to 1:1)
  8. customThen, it is purified again by means of HPLC

Sources & evidence

ORD record
ord-e15a3a2ed9c74c3eb45d50c2a40b913f
Source dataset
uspto-grants-2008_10
Patent number
US07442794B2

Reaction notes

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