HCID 66827699, compound → HCID 69810089, compound

HRID 1037749Notes

Reaction equation

HRID 1037749 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:9](=[O:33])[C:10]([NH:12][NH:13][C:14](=[O:32])[C:15]2[CH:20]=[CH:19][C:18]([O:21][CH2:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)=[C:17]([CH3:29])[C:16]=2[CH2:30][CH3:31])=[O:11])[CH:5]=[C:6]([F:8])[CH:7]=1>O1CCCC1.C1(C)C=CC=CC=1>[F:1][C:2]1[CH:3]=[C:4]([C@@H:9]([OH:33])[C:10]([NH:12][NH:13][C:14](=[O:32])[C:15]2[CH:20]=[CH:19][C:18]([O:21][CH2:22][C:23]3[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=3)=[C:17]([CH3:29])[C:16]=2[CH2:30][CH3:31])=[O:11])[CH:5]=[C:6]([F:8])[CH:7]=1

Participants

4

Reactant 1

HCID 66827699HCID 66827699, compound

Product 1

HCID 69810089HCID 69810089, compoundYield 20.8%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

302 mg of N′-[2-(3,5-difluorophenyl)-2-oxoacetyl]-4-benzyloxy-2-ethyl-3-methylbenzohydrazide (B3) are dissolved in 25 ml of tetrahydrofuran. This solution is added dropwise over the course of 5 min to a solution of 49 μl of borane/dimethyl sulfide complex and 55 μl of (R)-methyloxazaborolidine [(R)-Me-CBS, 1-1.5 M in toluene) in 17 ml of tetrahydrofuran at a temperature of (−)78° C. The cooling bath is subsequently removed, and the solution is stirred for 6 h, during which the reaction solution warms to room temperature: 100 ml of water are then added, and the mixture is extracted three times with 150 ml of ethyl acetate each time. The combined organic phases are washed with 40 ml of each of water, 0.1 M HCl and sat. NaCl solution, dried over NaSO4, filtered off with suction and evaporated to dryness. The residue is purified by means of preparative HPLC (solvent gradient: water/1-50% by vol. of acetonitrile), giving 63 mg of the title compound as colourless, amorphous solid. MS: 932 (2M+Na+); TLC: Rf=0.56 (cyclohexane/methyl tert-butyl ether 1:4, parts by volume).

Workup

  1. customThe cooling bath is subsequently removed
  2. customwarms to room temperature
  3. addition100 ml of water are then added
  4. extractionthe mixture is extracted three times with 150 ml of ethyl acetate each time
  5. washThe combined organic phases are washed with 40 ml of each of water, 0.1 M HCl and sat. NaCl solution
  6. dry with materialdried over NaSO4
  7. filtrationfiltered off with suction
  8. customevaporated to dryness
  9. customThe residue is purified by means of preparative HPLC (solvent gradient: water/1-50% by vol. of acetonitrile)

Sources & evidence

ORD record
ord-5186552498b846e8b28ebeb2052c0d26
Source dataset
uspto-grants-2013_10
Patent number
US08546613B2

Reaction notes

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