Sodium Carbonate → 5-(2-Fluoro-6-[1,2,3]triazol-2-yl-benzoyl)-hexahydro-pyrrolo[3,4-c]pyrrole-2-carboxylic acid tert-butyl ester

HRID 243841Notes

Reaction equation

HRID 243841 reaction equation
C(=O)([O-])[O-].[Na+].[Na+].[C:7]([O:11][C:12]([N:14]1[CH2:21][CH:20]2[CH:16]([CH2:17][NH:18][CH2:19]2)[CH2:15]1)=[O:13])([CH3:10])([CH3:9])[CH3:8].[F:22][C:23]1[CH:31]=[CH:30][CH:29]=[C:28]([N:32]2[N:36]=[CH:35][CH:34]=[N:33]2)[C:24]=1[C:25](Cl)=[O:26]>C1(C)C=CC=CC=1>[C:7]([O:11][C:12]([N:14]1[CH2:15][CH:16]2[CH:20]([CH2:19][N:18]([C:25](=[O:26])[C:24]3[C:28]([N:32]4[N:33]=[CH:34][CH:35]=[N:36]4)=[CH:29][CH:30]=[CH:31][C:23]=3[F:22])[CH2:17]2)[CH2:21]1)=[O:13])([CH3:10])([CH3:8])[CH3:9]

Participants

5

Reactant 3

HCID 10340Sodium Carbonate2×HCID 4142526Tert-butyl octahydropyrrolo(3,4-c)pyrrole-2-carboxylateHCID 866691682-Fluoro-6-[1,2,3]triazol-2-yl-benzoyl chloride

Product 1

HCID 671161965-(2-Fluoro-6-[1,2,3]triazol-2-yl-benzoyl)-hexahydro-pyrrolo[3,4-c]pyrrole-2-carboxylic acid tert-butyl esterYield 76.8%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
0 °C

Procedure

In a 3-neck round bottom 100 mL flask was added toluene (8.5 mL), aqueous sodium carbonate (1.42 g in 10.7 mL water), and Intermediate 15 (0.905 mg, 4.26 mmol). The biphasic mixture was cooled to 0° C. After cooling to 0° C., 2-fluoro-6-[1,2,3]triazol-2-yl-benzoyl chloride was poured over the stirring biphasic mixture of amine and aqueous sodium carbonate. An exotherm was observed. The mixture was allowed to warm to room temperature. After 1 h, a sample of the organic layer was quenched into methanol and a small amount of acid chloride was determined to remain (observed as its methyl ester). Additional amine (˜50 mg) was added and the mixture was stirred overnight at room temperature. At the end of this period, the layers were separated and 100 mL of methanol were added to the organic layer. The organic was concentrated and purified using flash column chromatography (FCC), gradient of 5-50% of a solution of 10% MeOH, 0.1% NH4OH in DCM/DCM. The desired fractions were combined and concentrated to provide a white foamy solid (1.327 g, 76.8%). MS (ESI): mass calculated for C20H24FN5O3, 401.44, m/z found 346.2 [M+H-56]+. 1H NMR (400 MHz, CDCl3): 7.91-7.73 (m, 3H), 7.53-7.39 (m, 1H), 7.18-7.06 (m, 1H), 4.00-2.76 (m, 10H), 1.52-1.33 (m, 9H).

Workup

  1. temperatureAfter cooling to 0° C.
  2. temperatureto warm to room temperature
  3. customa sample of the organic layer was quenched into methanol
  4. additionAdditional amine (˜50 mg) was added
  5. customAt the end of this period, the layers were separated
  6. addition100 mL of methanol were added to the organic layer
  7. concentrationThe organic was concentrated
  8. custompurified
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-c5f8cd914d6f4802aad66a791ce6cd56
Source dataset
uspto-grants-2014_02
Patent number
US08653263B2

Reaction notes

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