Morpholine → HCID 57528992, compound

HRID 1454043Notes

Reaction equation

HRID 1454043 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][C:10]([CH3:31])=[C:11]([CH2:13][CH2:14][O:15][C:16]3[CH:17]=[C:18]4[C:22](=[CH:23][CH:24]=3)[C@H:21]([CH2:25][C:26]([O:28][CH2:29][CH3:30])=[O:27])[CH2:20][CH2:19]4)[N:12]=2)=[CH:4][CH:3]=1.CC(C)([O-])C.[Na+].C1(C2C=CC=CC=2)C=CC=CC=1P(C(C)(C)C)C(C)(C)C.[NH:59]1[CH2:64][CH2:63][O:62][CH2:61][CH2:60]1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(C)C=CC=CC=1>[CH3:31][C:10]1[O:9][C:8]([C:5]2[CH:6]=[CH:7][C:2]([N:59]3[CH2:64][CH2:63][O:62][CH2:61][CH2:60]3)=[CH:3][CH:4]=2)=[N:12][C:11]=1[CH2:13][CH2:14][O:15][C:16]1[CH:17]=[C:18]2[C:22](=[CH:23][CH:24]=1)[C@H:21]([CH2:25][C:26]([O:28][CH2:29][CH3:30])=[O:27])[CH2:20][CH2:19]2

Participants

7

Reactant 4

HCID 8083MorpholineHCID 27342152-(Di-tert-butylphosphino)biphenylHCID 23676156Sodium t-butoxideHCID 69053646(1S)-(5-{2-[2-(4-bromo-phenyl)-5-methyl-oxazole-4-yl]-ethoxy}-indan-1-yl)-acetic acid ethyl ester

Product 1

HCID 57528992HCID 57528992, compoundYield 60%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

To a vacuum dried flask charged with argon were added ethyl ((1 S)-5-{2-[2-(4-bromophenyl)-5-methyl-1,3-oxazol-4-yl]ethoxy}-2,3-dihydro-1H-inden-1-yl )acetate (0.1 g, 0.2 mmol), sodium t-butoxide (0.03 g, 0.3 mmol), 1,1′-biphenyl-2-yl[di(tert-butyl)]phosphine (0.012 g, 0.04 mmol), morpholine (0.022 g, 0.25 mmol), Pd2(dba)3 (0.019 g, 0.02 mmol), and toluene (1 mL). The reaction was degassed by bubbling argon through the flask for 15 minutes. The reaction was stirred at 80° C. for 16 h, then was cooled to rt and filtered through a silica gel plug. The filtrate was evaporated under vacuum and the residue was purified by HPLC to obtain ethyl [(1S)-5-(2-{5-methyl-2-[4-(4-morpholinyl)phenyl]-1,3-oxazol-4-yl}ethoxy)-2,3-dihydro-1H-inden-1-yl]acetate (0.06 g, 0.1 mmol) in 60% yield. 1H NMR ( CDCl3) δ 1.3 (m, 3H), 1.7 (m, 1H), 2.4 (m, 5H), 2.8 (m, 3H), 3.0 (m, 2H), 3.3 (m, 4H), 3.5 (m, 1H), 3.9 (m, 4H), 4.2 (m, 4H), 6.7 (m, 2H), 6.9 (d, 2H), 7.1 (d, 1H), 7.9 (m, 2H); MS (ES) 491 (M+1)+.

Workup

  1. customTo a vacuum dried flask
  2. additioncharged with argon
  3. customThe reaction was degassed
  4. customby bubbling argon through the flask for 15 minutes
  5. temperaturewas cooled to rt
  6. filtrationfiltered through a silica gel plug
  7. customThe filtrate was evaporated under vacuum
  8. customthe residue was purified by HPLC

Sources & evidence

ORD record
ord-5599e074af564c9892d6bc4132750990
Source dataset
uspto-grants-2009_01
Patent number
US07476742B2

Reaction notes

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