Hydrogen Peroxide → HCID 56646611, compound

HRID 579197Notes

Reaction equation

HRID 579197 reaction equation
C[O:2][C:3]([C:5]1[S:6][C:7]([C:26]#[C:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[CH:8][C:9]=1[N:10]1[CH:15]([CH:16]2[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]2)[CH2:14][O:13][C@H:12]([CH2:22][CH:23]=[CH2:24])[C:11]1=[O:25])=[O:4].B1C2CCCC1CCC2.[OH-:41].[Na+].OO>C1COCC1.CCO>[CH:16]1([C@H:15]2[N:10]([C:9]3[CH:8]=[C:7]([C:26]#[C:27][C:28]([CH3:30])([CH3:29])[CH3:31])[S:6][C:5]=3[C:3]([OH:2])=[O:4])[C:11](=[O:25])[C@@H:12]([CH2:22][CH2:23][CH2:24][OH:41])[O:13][CH2:14]2)[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21]1.[CH:16]1([C@H:15]2[N:10]([C:9]3[CH:8]=[C:7]([C:26]#[C:27][C:28]([CH3:30])([CH3:29])[CH3:31])[S:6][C:5]=3[C:3]([OH:2])=[O:4])[C:11](=[O:25])[C@H:12]([CH2:22][CH2:23][CH2:24][OH:41])[O:13][CH2:14]2)[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21]1

Participants

8

Reactant 4

HCID 784Hydrogen PeroxideHCID 14798Sodium HydroxideHCID 789669-Borabicyclo(3.3.1)nonaneHCID 66684866HCID 66684866, compound

Product 2

HCID 56646611HCID 56646611, compoundHCID 56646612HCID 56646612, compound

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 3-((R)-2-Allyl-5-cyclohexyl-3-oxo-morpholin-4-yl)-5-(3,3-dimethyl-but-1-ynyl)-thiophene-2-carboxylic acid methyl ester (200 mg, 0.45 mmol, 1.0 equiv) in THF (4.0 mL) at 0° C. was added 9-BBN (2.2 mL, 0.5 M in THF, 1.1 mmol, 2.5 equiv) over 10 minutes and the resulting solution was stirred at room temperature for 18 hours. The solution was then cooled to 0° C. and to the solution was added EtOH, aq. NaOH. solution, aq. H2O2 solution. The reaction mixture was heated to reflux for 90 minutes. After cooled to room temperature, the reaction mixture was extracted with EtOAc. The organic layer was dried over Na2SO4 and the residue was purified by prep-HPLC to give product 3-[(2R,5R)-5-Cyclohexyl-2-(3-hydroxy-propyl)-3-oxo-morpholin-4-yl]-5-(3,3-dimethyl-but-1-ynyl)-thiophene-2-carboxylic acid (20 mg) and 3-[(2S,5R)-5-Cyclohexyl-2-(3-hydroxy-propyl)-3-oxo-morpholin-4-yl]-5-(3,3-dimethyl-but-1-ynyl)-thiophene-2-carboxylic acid (20 mg). The stereochemistry at 2 position of morpholinone has not been established. Product 1: MW: 448.3 [M+H]+. 1H-NMR (400 MHz, CD3OD): δ 6.93 (s, 1H), 4.14 (m, 1H), 4.0 (m, 1H), 3.62 (m, 1H), 3.58 (m, 2H), 2.02-1.48 (m, 10H), 1.32 (s, 9H), 1.25-1.17 (m, 6H). Product 2: MW: 448.3 [M+H]+. 1H-NMR (400 MHz, CD3OD): δ 6.97 (s, 1H), 4.13 (m, 1H), 3.90 (m, 1H), 3.82 (m, 1H), 3.57 (m, 2H), 1.97-1.48 (m, 10H), 1.32 (s, 9H), 1.26-1.09 (m, 6H).

Workup

  1. temperatureThe solution was then cooled to 0° C. and to the solution
  2. temperatureThe reaction mixture was heated
  3. temperatureto reflux for 90 minutes
  4. temperatureAfter cooled to room temperature
  5. extractionthe reaction mixture was extracted with EtOAc
  6. dry with materialThe organic layer was dried over Na2SO4
  7. customthe residue was purified by prep-HPLC

Sources & evidence

ORD record
ord-0b9809d85bb641cba41982dc6d828ebc
Source dataset
uspto-grants-2015_05
Patent number
US09040690B2

Reaction notes

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