Cesium carbonate → HCID 21034112, compound

HRID 1830726Notes

Reaction equation

HRID 1830726 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]1[CH2:13][CH2:12][NH:11][CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[F:14][C:15]1[CH:22]=[CH:21][C:18]([CH2:19]Br)=[CH:17][CH:16]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CCO>[C:1]([O:5][C:6]([NH:8][C@H:9]1[CH2:13][CH2:12][N:11]([CH2:19][C:18]2[CH:21]=[CH:22][C:15]([F:14])=[CH:16][CH:17]=2)[CH2:10]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 680214-Fluorobenzyl bromideHCID 1514396(3S)-(-)-3-(tert-Butoxycarbonylamino)pyrrolidine

Product 1

HCID 21034112HCID 21034112, compoundYield 77.4%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of (3S)-(+) -3-(tert-butoxycarbonylamino)pyrrolidine (410 mg, 2.20 mmol), in 22 mL EtOH, was added, (288 μL, 2.31 mmol) of 4-fluorobenzyl bromide, and (788 mg, 2.42 mmol) of finely powdered cesium carbonate. The stirred reaction mixture was heated at 80° C., under nitrogen for 3 h, after which time, TLC indicated the reaction was complete. The reaction was then concentrated in vacuo to about 5 mL, and was then diluted with 30 mL of EtOAc, and washed with 20 mL of 5% NH4OH. The aqueous fraction was extracted with diethyl ether (3×20 mL). The combined organics were washed with 20 mL of brine, dried (MgSO4), filtered and concentrated. The crude white solid was triturated with 1:1 ether-hexane to give 501 mg (77%) of the desired product as a white solid. 1H-NMR (400 MHz, CDCl3) δ7.2-7.3 (m, 2H), 6.9-7.1 (m, 2H), 4.85 (br. s, 1H, exchanges), 4.18 (br. s, 1H), 3.55 (s, 2H), 2.65 (br. m, 1H), 2.58 (n, 1H), 2.50 (m, 1H), 2.2-2.4 (m, 2H), 1.5-1.7, (m, 1H), 1.4 (s, 9H).

Workup

  1. customThe stirred reaction mixture
  2. concentrationThe reaction was then concentrated in vacuo to about 5 mL
  3. additionwas then diluted with 30 mL of EtOAc
  4. washwashed with 20 mL of 5% NH4OH
  5. extractionThe aqueous fraction was extracted with diethyl ether (3×20 mL)
  6. washThe combined organics were washed with 20 mL of brine
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude white solid was triturated with 1:1 ether-hexane

Sources & evidence

ORD record
ord-a7715fe4378f402196cf65cf58a62409
Source dataset
uspto-grants-2006_06
Patent number
US07067506B2

Reaction notes

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