3-Fluorophenol → HCID 53248398, compound

HRID 1845874Notes

Reaction equation

[NH2:1][C:2]1[N:7]=[C:6]([C@@H:8]([OH:10])[CH3:9])[CH:5]=[CH:4][N:3]=1.[F:11][C:12]1[CH:13]=[C:14](O)[CH:15]=[CH:16][CH:17]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>O1CCCC1>[F:11][C:12]1[CH:17]=[C:16]([CH:15]=[CH:14][CH:13]=1)[O:10][C@@H:8]([C:6]1[CH:5]=[CH:4][N:3]=[C:2]([NH2:1])[N:7]=1)[CH3:9]

Participants

Conditions

Temperature: 0 °C

Procedure

(S)-1-(2-aminopyrimidin-4-yl)ethanol (6b) (7.75 g), 3-fluorophenol (6.87 g) and triphenylphosphine (16.07 g) were added to tetrahydrofuran (150 mL) under nitrogen and cooled to 0° C. (brine/ice bath). The resulting brown mixture was stirred at 0° C. for 20 min then diisopropyl azodicarboxylate (12.06 mL, 12.39 g) was added dropwise as a solution in tetrahydrofuran (40 mL). The reaction was maintained at 0-2° C. throughout the addition and was then allowed to warm to room temperature overnight. The solvent was removed under reduced pressure before the crude product was loaded onto a silica plug and purified by flash chromatography on silica eluting with heptane/ethyl acetate 7:3 followed by crystallisation from ethanol to give the title compound (6.2 g) as a white crystalline solid, MS (ES): m/z 234.0 [M+H]+; [α]D−153.0 (methanol, c=1.8 mg/ml).

Workup

temperatureThe reaction was maintained at 0-2° C. throughout the addition
temperatureto warm to room temperature overnight
customThe solvent was removed under reduced pressure before the crude product
custompurified by flash chromatography on silica eluting with heptane/ethyl acetate 7:3
customfollowed by crystallisation from ethanol

Sources & evidence

ORD record: ord-ae219262030848d69f547b450d7389e5
Source dataset: uspto-grants-2015_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08952001B2

Reaction notes

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