4-Nitrobenzoic Acid → tert-butyl (8S,9aR)-8-[(4-nitrobenzoyl)oxy]-5-oxohexahydro-1H-pyrrolo[1,2-a][1,4]diazepine-2(3H)-carboxylate

HRID 572039Notes

Reaction equation

HRID 572039 reaction equation
[OH:1][C@H:2]1[CH2:19][N:5]2[C:6](=[O:18])[CH2:7][CH2:8][N:9]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:10][C@H:4]2[CH2:3]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[N+:39]([C:42]1[CH:50]=[CH:49][C:45]([C:46](O)=[O:47])=[CH:44][CH:43]=1)([O-:41])=[O:40].N(C(OC(C)C)=O)=NC(OC(C)C)=O>O1CCCC1>[N+:39]([C:42]1[CH:43]=[CH:44][C:45]([C:46]([O:1][C@@H:2]2[CH2:19][N:5]3[C:6](=[O:18])[CH2:7][CH2:8][N:9]([C:11]([O:13][C:14]([CH3:15])([CH3:16])[CH3:17])=[O:12])[CH2:10][C@H:4]3[CH2:3]2)=[O:47])=[CH:49][CH:50]=1)([O-:41])=[O:40]

Participants

6

Reactant 4

HCID 61084-Nitrobenzoic AcidHCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 86723190tert-butyl (8R,9aR)-8-hydroxy-5-oxohexahydro-1H-pyrrolo[1,2-a][1,4]diazepine-2(3H)-carboxylate

Product 1

HCID 86723191tert-butyl (8S,9aR)-8-[(4-nitrobenzoyl)oxy]-5-oxohexahydro-1H-pyrrolo[1,2-a][1,4]diazepine-2(3H)-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

tert-Butyl (8R,9aR)-8-hydroxy-5-oxohexahydro-1H-pyrrolo[1,2-a][1,4]diazepine-2(3H)-carboxylate (50 mg, 0.185 mmol, 1.0 equivalent, Part D), triphenylphosphine (60.6 mg, 0.231 mmol, 1.25 equivalents), and 4-nitrobenzoic acid (46.4 mg, 0.277 mmol, 1.5 equivalents) were dissolved in tetrahydrofuran (1.0 mL), and the resulting solution was cooled to −78° C. Diisopropyl azodicarboxylate (0.043 mL, 0.222 mmol, 1.2 equivalents) was dissolved in tetrahydrofuran (0.5 mL), and the resultant solution was added to the reaction mixture. The reaction mixture was removed from the cooling bath and warmed to room temperature for 0.5 hour. After the addition of 1 drop of saturated sodium bicarbonate, the tetrahydrofuran solution was loaded directly onto 2 sequentially linked 4 g silica gel cartridges, eluted with 50-100% ethyl acetate/heptanes over 20 minutes. The titled compound co-eluted with triphenylphosphine oxide and was used without additional purification (225 mg combined material). 1H NMR (400 MHz, CDCl3) δ ppm 8.28 (d, J=8.9 Hz, 2H), 8.15 (d, J=8.9 Hz, 2H), 5.52 (t, J=4.0 Hz, 1H), 4.53-3.94 (m, 4H), 3.73 (dd, J=14.1, 4.2 Hz, 1H), 3.02 (br s, 1H), 2.78-2.59 (m, 3H), 2.55 (dt, J=13.7, 7.0 Hz, 1H), 2.03-1.91 (m, 1H), 1.47 (s, 9H); MS (ESI+) m/z 419.8 (M+H)+.

Workup

  1. customThe reaction mixture was removed from the cooling bath
  2. temperaturewarmed to room temperature for 0.5 hour
  3. additionAfter the addition of 1 drop of saturated sodium bicarbonate
  4. washeluted with 50-100% ethyl acetate/heptanes over 20 minutes
  5. customwas used without additional purification (225 mg combined material)

Sources & evidence

ORD record
ord-4fe589690df04f70a64f308be36b16cc
Source dataset
uspto-grants-2015_05
Patent number
US09029361B2

Reaction notes

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