Lithium Chloride → 4-(2,6-dichloro-5-hydroxy-4-pyrimidinyl)-3-Morpholinemethanol

HRID 334138Notes

Reaction equation

[Cl:1][C:2]1[N:7]=[C:6]([N:8]2[CH2:13][CH2:12][O:11][CH2:10][CH:9]2[CH2:14][OH:15])[C:5]([O:16]C)=[C:4]([Cl:18])[N:3]=1.[Cl-].[Li+]>CN(C=O)C>[Cl:1][C:2]1[N:3]=[C:4]([Cl:18])[C:5]([OH:16])=[C:6]([N:8]2[CH2:13][CH2:12][O:11][CH2:10][CH:9]2[CH2:14][OH:15])[N:7]=1

Participants

Conditions

Temperature: 160 °C

Procedure

A mixture of [4-(2,6-dichloro-5-methoxy-pyrimidin-4-yl)-morpholin-3-yl]-methanol (614 mg, 2.09 mmol) and lithium chloride (246 mg, 5.80 mmol) in anhydrous DMF (5 mL) was heated at 160° C. for 10 mins in a microwave reactor, then concentrated in vacuo to give 2,4-dichloro-6-(3-hydroxymethyl-morpholin-4-yl)-pyrimidin-5-ol. DIAD (452 μL, 2.3 mmol) was added to a solution of 2,4-dichloro-6-(3-hydroxymethyl-morpholin-4-yl)-pyrimidin-5-ol (2 mmol) and triphenyl phosphine (603 mg, 2.3 mmol) in 1,4-dioxane (5 mL) and the mixture stirred at RT for 1 h, then concentrated in vacuo. The resulting residue was purified by column chromatography (SiO2, 0 to 50% ethyl acetate in cyclohexane) affording 1,3-Dichloro-5,6,8a,9-tetrahydro-8H-7,10-dioxa-2,4,4b-triaza-phenanthrene (200 mg, 37%). LCMS (method A): RT=2.91 min, [M+H]−=262/264.

Workup

concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-39e8b46f69ba4557a7e4e76a06b0d81f
Source dataset: uspto-grants-2014_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08883799B2

Reaction notes

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