Benzylamine → HCID 57529003, compound

HRID 1454040Notes

Reaction equation

HRID 1454040 reaction equation
C(=O)([O-])[O-].[Cs+].[Cs+].Br[C:8]1[CH:9]=[C:10]([C:15]2[O:16][C:17]([CH3:38])=[C:18]([CH2:20][CH2:21][O:22][C:23]3[CH:24]=[C:25]4[C:29](=[CH:30][CH:31]=3)[C@H:28]([CH2:32][C:33]([O:35][CH2:36][CH3:37])=[O:34])[CH2:27][CH2:26]4)[N:19]=2)[CH:11]=[CH:12][C:13]=1[CH3:14].[CH2:39]([NH2:46])[C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1>C1(C)C=CC=CC=1.C(OCC)(=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>[CH2:39]([NH:46][C:8]1[CH:9]=[C:10]([C:15]2[O:16][C:17]([CH3:38])=[C:18]([CH2:20][CH2:21][O:22][C:23]3[CH:24]=[C:25]4[C:29](=[CH:30][CH:31]=3)[C@H:28]([CH2:32][C:33]([O:35][CH2:36][CH3:37])=[O:34])[CH2:27][CH2:26]4)[N:19]=2)[CH:11]=[CH:12][C:13]=1[CH3:14])[C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1

Participants

8

Reactant 3

HCID 7504BenzylamineHCID 10796Cesium carbonateHCID 57528886HCID 57528886, compound

Product 1

HCID 57529003HCID 57529003, compoundYield 93.3%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 634876Binap, (A+-)-CatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
85 °C

Procedure

A dried flask was charged with palladium acetate (25.2 mg, 0.11 mmol, 5 mol %), BINAP (104.9 mg, 0.17 mmol, 7.5 mol %), and cesium carbonate (1.46 g, 4.49 mmol). To this mixture was added a solution of ethyl ((1S)-5-{2-[2-(3-bromo-4-methylphenyl)-5-methyl-1,3-oxazol-4-yl]ethoxy}-2,3-dihydro-1H-inden-1-yl)acetate (1.12 g, 2.25 mmol) and benzyl amine (0.48 g, 4.49 mmol) in toluene (50 mL) using an addition funnel. The first 15 mL was added quickly (5 minutes) and the remainder added over a period of 1 h. The mixture warmed to 85° C. after the first 30% portion was added. The reaction mixture was stirred at 85° C. for 16 h. The crude was cooled to rt, diluted with ethyl acetate, and then filtered through a Celite® plug. The filtrate was then concentrated under reduced pressure and the residue purified by silica gel flash chromatography (10-20% ethyl acetate in hexanes) to afford 1.1 g (93.3% yield) of desired product. 1H NMR (300 MHz/CDCl3) δ 7.28-7.44 (m, 7H), 7.12 (d, 1H), 7.03 (d, 1H), 6.77 (s, 1H), 6.71 (d, 1H), 4.44 (s, 2H), 4.13-4.22 (m, 4H), 3.82 (br, 1H), 3.51 (qr, 1H), 2.96 (t, 2H), 2.77-2.92 (m, 2H), 2.71 (dd, 1H), 2.31-2.43 (m, 5H), 2.17 (s, 3H), 1.61-1.79 (m, 1H), 1.26 (t, 3H). EI-LCMS(rel abundance), m/z 525.4 (MH+, 100%).

Workup

  1. additionThe first 15 mL was added quickly (5 minutes)
  2. additionthe remainder added over a period of 1 h
  3. additionwas added
  4. temperatureThe crude was cooled to rt
  5. filtrationfiltered through a Celite® plug
  6. concentrationThe filtrate was then concentrated under reduced pressure
  7. customthe residue purified by silica gel flash chromatography (10-20% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-d7a1285200144885ab41085d5e568e30
Source dataset
uspto-grants-2009_01
Patent number
US07476742B2

Reaction notes

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