Diazomethane → HCID 20767946, compound

HRID 2081122Notes

Reaction equation

[C:1]([O:5][C:6]([NH:8][C@:9]1([C:14]([O:16]CC)=[O:15])[CH2:11][C@H:10]1[CH:12]=[CH2:13])=[O:7])([CH3:4])([CH3:3])[CH3:2].[N+](=[CH2:21])=[N-]>CC([O-])=O.CC([O-])=O.[Pd+2].CCOCC>[C:1]([O:5][C:6]([NH:8][C@:9]1([C:14]([OH:16])=[O:15])[CH2:11][C@H:10]1[CH:12]1[CH2:13][CH2:21]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

Conditions

Temperature: -15 °C

Procedure

A 30 mL ether solution of (1R,2S)-ethyl 1-(tert-butoxycarbonylamino)-2-vinylcyclopropanecarboxylate (1.0 g, 3.9 mmol, prepared as described in WO2005037214) in a 500 mL round-bottomed flask equipped with a stir bar was first cooled in an acetone-ice bath to approx. −15° C., then an ether solution of diazomethane (33 ml, 20 mmol) was added in one portion to the above solution. While stirring vigorously and keeping the reaction open to air, Pd(OAc)2 (0.088 g, 0.39 mmol) was added to in one portion to the reaction at −15° C. After the active effervescence subsided, the reaction was allowed to stir for another 5 min at −15° C. and concentrated down to fairly clean crude product. The crude could be further purified with flash chromatography on silica (eluent=hexanes/EtOAc 5:1), giving the titled compound as a colorless thick oil (1.0 g, 95% yield). 1H-NMR (400 MHz, CDCl3) δ 5.10 (br s, 1 H), 4.18-4.24 (m, 2 H), 1.60-1.64 (m, 2 H), 1.44 (s, 9 H), 1.27 (t, 3 H), 1.05-1.11 (m, 1 H), 0.83-0.89 (m, 1H), 0.47-0.58 (m, 2 H), 0.30-0.34 (m, 2 H). LCMS (APCI+) 170.0 (MH+−Boc).

Workup

additionwas added to in one portion to the reaction at −15° C
stirringto stir for another 5 min at −15° C.
concentrationconcentrated down to fairly clean crude product
customThe crude could be further purified with flash chromatography on silica (eluent=hexanes/EtOAc 5:1)

Sources & evidence

ORD record: ord-4020101e99104368bbc6eb5cb472d560
Source dataset: uspto-grants-2011_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07932277B2

Reaction notes

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