Methyl morpholine oxide → 3-cyano-N-[(2S)-2-(4-fluorophenyl)-4-oxobutyl]-N-methyl-5,6,7,8-tetrahydronaphthalene-1-carboxamide

HRID 749451Notes

Reaction equation

HRID 749451 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([C:13]([N:15]([CH2:17][C@H:18]([C:22]2[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=2)[CH2:19][CH:20]=C)[CH3:16])=[O:14])[C:6]2[CH2:7][CH2:8][CH2:9][CH2:10][C:11]=2[CH:12]=1)#[N:2].C[N+]1([O-])CC[O:33]CC1.OS([O-])=O.[Na+].I([O-])(=O)(=O)=O.[Na+]>CC(C)=O.C(O)(C)(C)C.O.[Cl-].[Na+].O.O=[Os](=O)(=O)=O>[C:1]([C:3]1[CH:4]=[C:5]([C:13]([N:15]([CH2:17][C@H:18]([C:22]2[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=2)[CH2:19][CH:20]=[O:33])[CH3:16])=[O:14])[C:6]2[CH2:7][CH2:8][CH2:9][CH2:10][C:11]=2[CH:12]=1)#[N:2]

Participants

10

Reactant 4

HCID 82029Methyl morpholine oxideHCID 23665763Sodium BisulfiteHCID 23667635Sodium periodateHCID 689785133-cyano-N-[(2S)-2-(4-fluorophenyl)pent-4-en-1-yl]-N-methyl-5,6,7,8-tetrahydronaphthalene-1-carboxamide

Product 1

HCID 113264143-cyano-N-[(2S)-2-(4-fluorophenyl)-4-oxobutyl]-N-methyl-5,6,7,8-tetrahydronaphthalene-1-carboxamideYield 89.9%

Reagents, catalysts & solvents 5

HCID 30318Osmium TetroxideCatalystHCID 180AcetoneSolventHCID 962WaterSolvent3×HCID 6386tert-ButanolSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

3-Cyano-N-[(2S)-2-(4-fluorophenyl)pent-4-en-1-yl]-N-methyl-5,6,7,8-tetrahydronaphthalene-1-carboxamide (460 mg, 1.22 mmol) was dissolved in a mixture of acetone (8 mL), t-butyl alcohol (4 mL) and water (2 mL) under nitrogen. OsO4 (2.5% in t-butyl alcohol, 0.165 mL, 0.01 mmol) was added together with 4-methylmorpholine-4-oxide (630 mg, 5.4 mmol). The solution was stirred at room temperature for 5 h and then an aqueous solution of NaHSO3 (39%, 12 mL) was added. The mixture was stirred for 15 min, diluted with water (50 mL) and then extracted three times with CH2Cl2. The organic solution was dried over Na2SO4 and then the solvent was evaporated. The residue (570 mg) is was dissolved in a mixture of THF (7 mL) and water (3 mL) and to the resultant solution was added sodium periodate (287 mg, 1.34 mmol). The mixture was stirred at room temperature overnight, diluted with water (50 mL) and brine (30 mL) and then extracted twice with CH2Cl2. The organic solution was dried over Na2SO4 and then the solvent was evaporated. There was obtained 415 mg (89%) of 3-cyano-N-[(2S)-2-(4-fluorophenyl)-4-oxobutyl]-N-methyl-5,6,7,8-tetrahydronaphthalene-1-carboxamide as an oil. 1H NMR (400 MHz, CDCl3): 1.4-4.2 (cm, 16H), 6.6-7.4 (cm, 6H), 9.7 (s, 1H); LCMS: m/z 379 (M+1)+.

Workup

  1. stirringThe mixture was stirred for 15 min
  2. extractionextracted three times with CH2Cl2
  3. dry with materialThe organic solution was dried over Na2SO4
  4. customthe solvent was evaporated
  5. dissolutionThe residue (570 mg) is was dissolved in a mixture of THF (7 mL) and water (3 mL) and to the resultant solution
  6. stirringThe mixture was stirred at room temperature overnight
  7. extractionextracted twice with CH2Cl2
  8. dry with materialThe organic solution was dried over Na2SO4
  9. customthe solvent was evaporated

Sources & evidence

ORD record
ord-3a206ef5c9904d9d8aeb47a1886a68be
Source dataset
uspto-grants-2008_07
Patent number
US07402581B2

Reaction notes

Loading…