Nitrogen → 2-[5-(2-Methyl-[1,3]dioxolan-2-yl)-thiophen-2-ylmethyl]-oxazole-4-carboxylic acid methyl ester

HRID 1189401Notes

Reaction equation

HRID 1189401 reaction equation
N#N.C1N2CN3CN(C2)CN1C3.C1CCN2C(=NCCC2)CC1.[CH3:24][O:25][C:26]([CH:28]1[CH2:32][O:31][C:30]([CH2:33][C:34]2[S:35][C:36]([C:39]3([CH3:44])[O:43][CH2:42][CH2:41][O:40]3)=[CH:37][CH:38]=2)=[N:29]1)=[O:27]>C(Cl)Cl.[Cu](Br)Br>[CH3:24][O:25][C:26]([C:28]1[N:29]=[C:30]([CH2:33][C:34]2[S:35][C:36]([C:39]3([CH3:44])[O:43][CH2:42][CH2:41][O:40]3)=[CH:37][CH:38]=2)[O:31][CH:32]=1)=[O:27]

Participants

7

Reactant 4

HCID 947NitrogenHCID 4101HexamethylenetetramineHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 671284352-[5-(2-Methyl-[1,3]dioxolan-2-yl)-thiophen-2-ylmethyl]-4,5-dihydro-oxazole-4-carboxylic acid methyl ester

Product 1

HCID 671285542-[5-(2-Methyl-[1,3]dioxolan-2-yl)-thiophen-2-ylmethyl]-oxazole-4-carboxylic acid methyl ester

Reagents, catalysts & solvents 2

HCID 24611Copper bromide (CuBr2)CatalystHCID 6344DichloromethaneSolvent

Procedure

In a flame dried round-bottomed flask equipped with a magnetic stir bar and under inert atmosphere (N2), hexamethylenetetramine (273 mg, 1.92 mmol) and DBU (0.29 mL, 1.92 mmol) were added to a stirred suspension of copper (II) bromide (429 mg, 1.92 mmol) in deoxygenated dry CH2Cl2 (2.0 mL). After 20 min, a deoxygenated solution of 2-[5-(2-methyl-[1,3]dioxolan-2-yl)-thiophen-2-ylmethyl]-4,5-dihydro-oxazole-4-carboxylic acid methyl ester (240 mg, 0.77 mmol) in CH2Cl2 (5.0 mL) was added and the reaction mixture was stirred at rt for 2 h. The solvent was removed under reduced pressure and the residue was partitioned between EA (60 mL), and 40 mL of a 1:1 mixture of sat. aq. NH4Cl and 25% aq. NH4OH. The aq. layer was extracted with EA (40 mL) and the combined organic layers were washed with 40 mL of a 1:1 mixture of sat. aq. NH4Cl and 25% aq. NH4OH followed by 10% citric acid (40 mL), sat. aq. NaHCO3 (40 mL) and brine (40 mL). The organic phase was dried over MgSO4, filtered, and the solvent was removed under reduced pressure. Purification of the residue by FC (2:1→1:4 hept-EA) gave the title compound as a pale yellow oil. TLC: rf (1:3 hept-EA)=0.40. LC-MS-conditions 01: tR=0.88 min, [M+H]+=309.98.

Workup

  1. customin deoxygenated dry CH2Cl2 (2.0 mL)
  2. customThe solvent was removed under reduced pressure
  3. customthe residue was partitioned between EA (60 mL), and 40 mL of a 1:1 mixture of sat. aq. NH4Cl and 25% aq. NH4OH
  4. extractionThe aq. layer was extracted with EA (40 mL)
  5. washthe combined organic layers were washed with 40 mL of a 1:1 mixture of sat. aq. NH4Cl and 25% aq. NH4OH
  6. dry with materialThe organic phase was dried over MgSO4
  7. filtrationfiltered
  8. customthe solvent was removed under reduced pressure
  9. customPurification of the residue by FC (2:1→1:4 hept-EA)

Sources & evidence

ORD record
ord-68316f6cb59342ce96d1d427cafd177f
Source dataset
uspto-grants-2014_03
Patent number
US08674111B2

Reaction notes

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