Lithium Chloride → 2,4-dichloro-6-((S)-2-hydroxymethyl-pyrrolidin-1-yl)-pyrimidin-5-ol

HRID 334143Notes

Reaction equation

[Cl:1][C:2]1[N:7]=[C:6]([N:8]2[CH2:12][CH2:11][CH2:10][C@H:9]2[CH2:13][OH:14])[C:5]([O:15]C)=[C:4]([Cl:17])[N:3]=1.[Cl-].[Li+]>CN(C=O)C>[Cl:1][C:2]1[N:3]=[C:4]([Cl:17])[C:5]([OH:15])=[C:6]([N:8]2[CH2:12][CH2:11][CH2:10][C@H:9]2[CH2:13][OH:14])[N:7]=1

Participants

Conditions

Temperature: 160 °C

Procedure

A mixture of [(S)-1-(2,6-dichloro-5-methoxy-pyrimidin-4-yl)-pyrrolidin-2-yl]-methanol (900 mg, 3.24 mmol) and lithium chloride (360 mg, 8.48 mmol) in anhydrous DMF (10 mL) was heated at 160° C. for 10 mins in a microwave reactor, then concentrated in vacuo to give 2,4-dichloro-6-((S)-2-hydroxymethyl-pyrrolidin-1-yl)-pyrimidin-5-ol. DIAD (700 μL, 3.56 mmol) was added to a solution of 2,4-dichloro-6-((S)-2-hydroxymethyl-pyrrolidin-1-yl)-pyrimidin-5-ol (3 mmol) and triphenyl phosphine (900 mg, 3.43 mmol) in 1,4-dioxane (10 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 20% ethyl acetate in cyclohexane) affording (S)-6,8-dichloro-2,3,3a,4-tetrahydro-1H-5-oxa-7,9,9b-triaza-cyclopenta[a]naphthalene. LCMS (method A): RT=2.98 min, [M+H]−=246/248.

Workup

concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-1916f495d7d34c1984e22b63c42410f5
Source dataset: uspto-grants-2014_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08883799B2

Reaction notes

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