Methanamine, N-methoxy-, hydrochloride (1:1) → HCID 87542905, compound

HRID 1619213Notes

Reaction equation

CO[C:3]([CH:5]1[CH2:8][N:7]([C:9]2[N:14]=[CH:13][CH:12]=[CH:11][N:10]=2)[CH2:6]1)=[O:4].Cl.[CH3:16][NH:17][O:18][CH3:19].C([Mg]Cl)(C)C>C1COCC1>[CH3:19][O:18][N:17]([CH3:16])[C:3]([CH:5]1[CH2:6][N:7]([C:9]2[N:10]=[CH:11][CH:12]=[CH:13][N:14]=2)[CH2:8]1)=[O:4]

Participants

Conditions

Temperature: -10 °C

Procedure

To a suspension of the above ester (137.3 mg, 0.711 mmol) and N-methyl-O-methyl hydroxylamine hydrochloride (127.6 mg, 1.103 mmol) in THF (5 ml), was added iso-propyl magnesium chloride (2.0 M in THF, 1.067 ml, 2.133 mmol) at −20° C. during 15 minutes. The mixture was stirred at −10° C. for another 30 minutes before it was quenched with the addition of saturated ammonium chloride (10 ml). The mixture was extracted with EtOAc (2×15 ml). The combined organic layers were washed with brine (10 ml), dried (MgSO4), filtered, and concentrated under reduced pressure to furnish the crude product. This material was purified by column chromatography (4% MeOH/CH2Cl2) to give 1-pyrimidin-2-yl-azetidine-3-carboxylic acid methoxy-methyl-amide (385.9 mg, 98%) as a white solid: 1H NMR (CDCl3, 400 MHz) δ 8.32 (d, J=6.4 Hz, 2H), 6.55 (t, J=6.4 Hz, 1H), 4.34 (m, 4H), 3.88 (m, 1H), 3.70 (s, 3H), 3.23 (s, 3H).

Workup

customwas quenched with the addition of saturated ammonium chloride (10 ml)
extractionThe mixture was extracted with EtOAc (2×15 ml)
washThe combined organic layers were washed with brine (10 ml)
dry with materialdried (MgSO4)
filtrationfiltered
concentrationconcentrated under reduced pressure
customto furnish the crude product
customThis material was purified by column chromatography (4% MeOH/CH2Cl2)

Sources & evidence

ORD record: ord-8b4897019f3143239458a1608ae4a539
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08772291B2

Reaction notes

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