Morpholine → HCID 24800687, compound

HRID 386455Notes

Reaction equation

HRID 386455 reaction equation
[CH:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:14]=[CH:13][C:12]([CH2:15][CH2:16][C:17]([C:19]3[O:20][C:21]([C:24]4[N:29]=[C:28]([C:30]([O:32][CH3:33])=[O:31])[CH:27]=[CH:26][CH:25]=4)=[CH:22][N:23]=3)=[O:18])=[CH:11][CH:10]=2)=[CH:5][CH:4]=1)=O.[NH:34]1[CH2:39][CH2:38][O:37][CH2:36][CH2:35]1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>ClC(Cl)C>[O:37]1[CH2:38][CH2:39][N:34]([CH2:1][C:3]2[CH:8]=[CH:7][C:6]([C:9]3[CH:10]=[CH:11][C:12]([CH2:15][CH2:16][C:17]([C:19]4[O:20][C:21]([C:24]5[N:29]=[C:28]([C:30]([O:32][CH3:33])=[O:31])[CH:27]=[CH:26][CH:25]=5)=[CH:22][N:23]=4)=[O:18])=[CH:13][CH:14]=3)=[CH:5][CH:4]=2)[CH2:35][CH2:36]1

Participants

5

Reactant 3

HCID 8083MorpholineHCID 5049666Sodium triacetoxyborohydrideHCID 86645815HCID 86645815, compound

Product 1

HCID 24800687HCID 24800687, compoundYield 58.6%

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Procedure

Methyl 6-(2-(3-(4′-formylbiphenyl-4-yl)propanoyl)oxazol-5-yl)pyridine-2-carboxylate (31 mg, 0.070 mmol) and morpholine (0.012 mL, 1.4 mmol) were dissolved in dichloroethane (2 mL) and NaBH(OAc)3 (31 mg, 15 mmol) was added. The reaction solution was stirred under an atmosphere of Ar at ambient temperature for 7 h and then quenched with saturated aqueous NaHCO3. The crude product was extracted with EtOAc and the solvent was removed in vacuo. The crude product was purified by flash chromatography (SiO2, 50-100% EtOAc/hexanes) to furnish methyl 6-(2-(3-(4′-(morpholinomethyl)biphenyl-4-yl)propanoyl)oxazol-5-yl)pyridine-2-carboxylate as a light yellow oil (21 mg, 58%): 1H NMR (CDCl3, 600 MHz) δ 8.12 (d, 1H, J=7.7 Hz), 8.04-8.02 (m, 2H), 7.97 (t, 1H, J=7.8 Hz), 7.52 (d, 4H, J=8.0 Hz), 7.38 (d, 2H, J=8.0 Hz), 7.34 (d, 2H, J=8.0 Hz), 4.04 (s, 3H), 3.73 (t, 4H, J=4.5 Hz), 3.54 (s, 2H), 3.51 (t, 2H, J=7.6 Hz), 3.16 (t, 2H, J=7.6 Hz), 2.48 (s, 4H); 13C NMR (CDCl3, 150 MHz) δ 187.3, 165.1, 157.4, 152.4, 148.5, 146.5, 139.8, 139.3, 139.0, 138.2, 136.7, 129.6, 128.9, 128.0, 127.1, 126.8, 125.2, 123.3, 67.0, 63.1, 53.6, 53.1, 40.6, 29.3; HR ESI-TOF m/z 512.2173 (M+H+, C30H29N3O5, requires 512.2180).

Workup

  1. customquenched with saturated aqueous NaHCO3
  2. extractionThe crude product was extracted with EtOAc
  3. customthe solvent was removed in vacuo
  4. customThe crude product was purified by flash chromatography (SiO2, 50-100% EtOAc/hexanes)

Sources & evidence

ORD record
ord-5db1455b99f54d9d872f37ac59ab64ef
Source dataset
uspto-grants-2013_02
Patent number
US08372823B2

Reaction notes

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