Isobutanol → (R)-tert-Butyl 2-((R)-(4-isobutoxyphenyl)((S)-2-phenylpropanamido)methyl)pyrrolidine-1-carboxylate

HRID 1874650Notes

Reaction equation

[CH3:1][CH:2]([CH3:5])[CH2:3][OH:4].CCOC(/N=N/C(OCC)=O)=O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O[C:38]1[CH:43]=[CH:42][C:41]([C@@H:44]([NH:57][C:58](=[O:67])[C@H:59]([C:61]2[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=2)[CH3:60])[C@H:45]2[CH2:49][CH2:48][CH2:47][N:46]2[C:50]([O:52][C:53]([CH3:56])([CH3:55])[CH3:54])=[O:51])=[CH:40][CH:39]=1>C1COCC1>[CH2:3]([O:4][C:38]1[CH:39]=[CH:40][C:41]([C@@H:44]([NH:57][C:58](=[O:67])[C@H:59]([C:61]2[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=2)[CH3:60])[C@H:45]2[CH2:49][CH2:48][CH2:47][N:46]2[C:50]([O:52][C:53]([CH3:56])([CH3:54])[CH3:55])=[O:51])=[CH:42][CH:43]=1)[CH:2]([CH3:5])[CH3:1]

Participants

Conditions

Temperature: 140 °C

Procedure

A solution of 2-methyl-1-propanol (6.52 μL, 0.071 mmol), DEAD (11.19 μL, 0.071 mmol), and triphenylphosphine (18.53 mg, 0.071 mmol) in THF (520 μL) in a microwave vial was stirred at room temperature for 10 min. (R)-tert-Butyl 2-((R)-(4-hydroxyphenyl)((S)-2-phenylpropanamido)methyl)pyrrolidine-1-carboxylate (30 mg, 0.071 mmol) was added and the solution heated at 140° C. in a microwave (Biotage) for 20 min. The crude mixture was filtered through a plug of silica gel eluting with 50% EtOAc in hexanes. The filtrate was concentrated in vacuo and carried directly into the next reaction. LRMS (ESI) m/e 481.50 [(M+H)+, calcd for C29H41N2O4 481.31].

Workup

additionwas added
filtrationThe crude mixture was filtered through a plug of silica gel eluting with 50% EtOAc in hexanes
concentrationThe filtrate was concentrated in vacuo
customcarried directly into the next reaction

Sources & evidence

ORD record: ord-37af9dffaaf34b25a7b8166bebf42127
Source dataset: uspto-grants-2012_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08304577B2

Reaction notes

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