4-Nitrobenzoic Acid → (8S,9aS)-5-oxo-2-[5-(trifluoromethyl)pyridin-2-yl]octahydro-1H-pyrrolo[1,2-a][1,4]diazepin-8-yl 4-nitrobenzoate

HRID 1050302Notes

Reaction equation

HRID 1050302 reaction equation
[OH:1][C@H:2]1[CH2:22][N:5]2[C:6](=[O:21])[CH2:7][CH2:8][N:9]([C:11]3[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:13][N:12]=3)[CH2:10][C@@H:4]2[CH2:3]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[N+:42]([C:45]1[CH:53]=[CH:52][C:48]([C:49](O)=[O:50])=[CH:47][CH:46]=1)([O-:44])=[O:43].N(C(OC(C)C)=O)=NC(OC(C)C)=O>O1CCCC1.O.C(OCC)(=O)C>[N+:42]([C:45]1[CH:46]=[CH:47][C:48]([C:49]([O:1][C@@H:2]2[CH2:22][N:5]3[C:6](=[O:21])[CH2:7][CH2:8][N:9]([C:11]4[CH:16]=[CH:15][C:14]([C:17]([F:19])([F:20])[F:18])=[CH:13][N:12]=4)[CH2:10][C@@H:4]3[CH2:3]2)=[O:50])=[CH:52][CH:53]=1)([O-:44])=[O:43]

Participants

8

Reactant 4

HCID 61084-Nitrobenzoic AcidHCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 86723180(8R,9aS)-8-hydroxy-2-[5-(trifluoromethyl)pyridin-2-yl]octahydro-5H-pyrrolo[1,2-a][1,4]diazepin-5-one

Product 1

HCID 86723183(8S,9aS)-5-oxo-2-[5-(trifluoromethyl)pyridin-2-yl]octahydro-1H-pyrrolo[1,2-a][1,4]diazepin-8-yl 4-nitrobenzoateYield 94%

Reagents, catalysts & solvents 3

HCID 962WaterCatalystHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-78 °C

Procedure

(8R,9aS)-8-Hydroxy-2-[5-(trifluoromethyl)pyridin-2-yl]octahydro-5H-pyrrolo[1,2-a][1,4]diazepin-5-one (100 mg, 0.317 mmol, Part B), triphenylphosphine (104 mg, 0.396 mmol), and 4-nitrobenzoic acid (80 mg, 0.476 mmol) were dissolved in tetrahydrofuran (2 mL), and the resulting solution was cooled to −78° C. Diisopropyl azodicarboxylate (77 mg, 0.381 mmol) in tetrahydrofuran (0.5 mL) was added. The mixture was warmed to room temperature and stirred for two hours. Then 1 drop of water was added. The mixture was purified by chromatography on silica gel (ethyl acetate/heptanes=1:1 then 100% ethyl acetate) to give 138 mg (94% yield) of the titled compound as a solid. 1H NMR (400 MHz, CDCl3) δ ppm 2.20 (m, 1H), 2.77 (m, 3 H), 3.33 (m, 1 H), 3.47 (m, 1 H), 3.88 (m, 1 H), 4.00 (m, 1H), 4.12 (m, 1H), 4.37 (m, 1H), 4.77 (dd, J=14, 4 Hz, 1 H), 5.54 (m, 1H), 6.67 (d, J=8 Hz, 1H), 7.69 (d, J=8 Hz, 1 H), 8.20 (d, J=8 Hz, 2 H), 8.35 (d, J=8 Hz, 2 H), 8.42 (s, 1 H); MS (ESI) m/z 465.0 (M+H)+.

Workup

  1. temperatureThe mixture was warmed to room temperature
  2. customThe mixture was purified by chromatography on silica gel (ethyl acetate/heptanes=1:1

Sources & evidence

ORD record
ord-5228da098b884afa8a122a5a51007765
Source dataset
uspto-grants-2016_07
Patent number
US09382258B2

Reaction notes

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