Morpholine → Cyclopropyl-(2,4-dichloro-6-morpholin-4-yl-pyrimidin-5-yloxy)-acetic acid methyl ester

HRID 528473Notes

Reaction equation

[CH3:1][O:2][C:3](=[O:18])[CH:4]([CH:15]1[CH2:17][CH2:16]1)[O:5][C:6]1[C:7](Cl)=[N:8][C:9]([Cl:13])=[N:10][C:11]=1[Cl:12].C(N(CC)CC)C.[NH:26]1[CH2:31][CH2:30][O:29][CH2:28][CH2:27]1>>[CH3:1][O:2][C:3](=[O:18])[CH:4]([CH:15]1[CH2:17][CH2:16]1)[O:5][C:6]1[C:11]([Cl:12])=[N:10][C:9]([Cl:13])=[N:8][C:7]=1[N:26]1[CH2:31][CH2:30][O:29][CH2:28][CH2:27]1

Participants

Reactant 3

HCID 8083Morpholine

HCID 8471Triethylamine

HCID 86711755Cyclopropyl-(2,4,6-trichloro-pyrimidin-5-yloxy)-acetic acid methyl ester

Product 1

HCID 86711756Cyclopropyl-(2,4-dichloro-6-morpholin-4-yl-pyrimidin-5-yloxy)-acetic acid methyl esterYield 89.3%

Procedure

To a suspension of cyclopropyl-(2,4,6-trichloro-pyrimidin-5-yloxy)-acetic acid methyl ester (224 mg, 0.72 mmol) in IMS (4 mL) was added triethylamine (150 μL, 1.08 mmol) followed by morpholine (63 μL, 0.72 mmol). The yellow solution was stirred for 2.5 hours at RT before being concentrated in vacuo. The resultant residue was purified by column chromatography (SiO2, gradient 0-20% ethyl acetate in cyclohexane) affording Cyclopropyl-(2,4-dichloro-6-morpholin-4-yl-pyrimidin-5-yloxy)-acetic acid methyl ester as a colourless gum (233 mg, 89%). 1H NMR (CDCl3): δ 3.99 (1H, d, J=9.54 Hz), 4.03-3.83 (4H, m), 3.80-3.75 (4H, m), 3.78 (3H, s), 1.32-1.21 (1H, m), 0.70-0.57 (2H, m), 0.52-0.45 (1H, m), 0.33-0.26 (1H, m).

Workup

concentrationbefore being concentrated in vacuo
customThe resultant residue was purified by column chromatography (SiO2, gradient 0-20% ethyl acetate in cyclohexane)

Sources & evidence

ORD record: ord-2e3801d9866240c5a7a1c522f4271719
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09346817B2

Reaction notes

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