Dimethylformamide → 3-(Methoxymethylcarbamoyl)pyrrolidine-1-carboxylic acid t-butyl ester

HRID 1427728Notes

Reaction equation

[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH:10]([C:13]([OH:15])=O)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C[N:17]([C:19]([O:23]N1N=NC2C=CC(=CC1=2)Cl)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH:41]1C=CC2N(O)N=NC=2C=1.Cl.CNOC.CN(C=O)C.CCN(C(C)C)C(C)C>C([O-])(O)=O.[Na+]>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH:10]([C:13](=[O:15])[NH:17][CH2:19][O:23][CH3:41])[CH2:9]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

Conditions

Temperature: 0 °C

Procedure

Pyrrolidine-1,3-dicarboxylic acid 1-t-butyl ester (0.7 g, 3.3 mmol), HCTU (2.0 g, 4.9 mmol), and HOBt (747 mg, 4.9 mmol), N,O-dimethylhydroxylamine HCl (1.6 g, 16.3 mmol) and DMF (10.0 mL, 129 mmol) were combined and cooled at 0° C. using an ice bath. DIPEA (5.7 mL, 32.5 mmol) was added slowly over 5 minutes. The mixture was allowed to warm to room temperature and stirred for 15 hours. The mixture was then diluted with sat. NaHCO3 (75 mL) and extracted with EtOAc (2×100 mL). The combined organic layers were washed with sat. NaCl (50 mL), dried over Na2SO4, filtered, concentrated under high vacuum to yield 2.9 g of the crude title compound as a mixture of the (R) and (S) enantiomers.

Workup

temperatureto warm to room temperature
extractionextracted with EtOAc (2×100 mL)
washThe combined organic layers were washed with sat. NaCl (50 mL)
dry with materialdried over Na2SO4
filtrationfiltered
concentrationconcentrated under high vacuum

Sources & evidence

ORD record: ord-4207147ebe71401d8f39ce1a6f851655
Source dataset: uspto-grants-2015_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08933249B2

Reaction notes

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