tert-Butanol → [5-Oxo-1-(3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl)pyrrolidin-3-yl]carbamic acid tert-butyl ester

HRID 1846993Notes

Reaction equation

HRID 1846993 reaction equation
[O:1]=[C:2]1[N:6]([C:7]2[CH:8]=[CH:9][C:10]3[O:15][CH2:14][C:13](=[O:16])[NH:12][C:11]=3[CH:17]=2)[CH2:5][CH:4](C(O)=O)[CH2:3]1.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:28])C=CC=CC=1.C([N:40]([CH2:43]C)CC)C.[C:45]([OH:49])([CH3:48])([CH3:47])[CH3:46]>>[C:45]([O:49][C:43](=[O:28])[NH:40][CH:4]1[CH2:3][C:2](=[O:1])[N:6]([C:7]2[CH:8]=[CH:9][C:10]3[O:15][CH2:14][C:13](=[O:16])[NH:12][C:11]=3[CH:17]=2)[CH2:5]1)([CH3:48])([CH3:47])[CH3:46]

Participants

5

Reactant 4

HCID 6386tert-ButanolHCID 8471TriethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 867249245-Oxo-1-(3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl)pyrrolidin-3-carboxylic acid

Product 1

HCID 86724925[5-Oxo-1-(3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl)pyrrolidin-3-yl]carbamic acid tert-butyl esterYield 61%

Procedure

A mixture of 5-oxo-1-(3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl)pyrrolidin-3-carboxylic acid (300 mg, 1.09 mmol), diphenyl phosphoryl azide (351 μl, 1.63 mmol), triethylamine (380 μl, 2.73 mmol) and tert-butyl alcohol (10 ml) was heated under reflux for 24 hours. The reaction solution was cooled, the solvent was then removed under reduced pressure, and the obtained residue was suspended in ethyl acetate to collect the insoluble material by filtration. The obtained residue was purified by silica gel column chromatography (chloroform/methanol) to yield 230 mg (61%) of the title compound in the form of a colorless solid.

Workup

  1. temperaturewas heated
  2. temperatureunder reflux for 24 hours
  3. temperatureThe reaction solution was cooled
  4. customthe solvent was then removed under reduced pressure
  5. customto collect the insoluble material
  6. filtrationby filtration
  7. customThe obtained residue was purified by silica gel column chromatography (chloroform/methanol)

Sources & evidence

ORD record
ord-c95225bd4b8642a38dc0a195e473730c
Source dataset
uspto-grants-2015_02
Patent number
US08952010B2

Reaction notes

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