N-bromobutanimide → tert-Butyl 3-(7-bromo-2H-benzo[b][1,4]thiazin-4(3H)-yl)pyrrolidine-1-carboxylate

HRID 424588Notes

Reaction equation

HRID 424588 reaction equation
[S:1]1[CH2:6][CH2:5][N:4]([CH:7]2[CH2:11][CH2:10][N:9]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:8]2)[C:3]2[CH:19]=[CH:20][CH:21]=[CH:22][C:2]1=2.[Br:23]N1C(=O)CCC1=O>CN(C=O)C.O>[Br:23][C:21]1[CH:20]=[CH:19][C:3]2[N:4]([CH:7]3[CH2:11][CH2:10][N:9]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:8]3)[CH2:5][CH2:6][S:1][C:2]=2[CH:22]=1

Participants

5

Reactant 2

HCID 67184N-bromobutanimide3×HCID 59144136tert-Butyl 3-(2H-benzo[b][1,4]thiazin-4(3H)-yl)pyrrolidine-1-carboxylate

Product 1

HCID 59144137tert-Butyl 3-(7-bromo-2H-benzo[b][1,4]thiazin-4(3H)-yl)pyrrolidine-1-carboxylateYield 120.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent4×

Procedure

A solution of tert-butyl 3-(2H-benzo[b][1,4]thiazin-4(3H)-yl)pyrrolidine-1-carboxylate (0.41 g, 1.302 mmol) in DMF (5 mL), was cooled to 0° C. and treated dropwise with N-bromosuccinimide (0.17 g, 0.977 mmol) in DMF (5 mL) for 15 minutes. The reaction was kept at 0° C. and was stirred for 1 hour at this temperature. At this time, N-bromosuccinimide (0.023 g, 0.130 mmol) in DMF (1 mL) was added dropwise to the reaction, which was then stirred for 1 hour at 0° C. The solution was treated again with N-bromosuccinimide (0.023 g, 0.130 mmol) in DMF (1 mL) and was stirred for 1 hour at 0° C. The solution was diluted in water (100 mL) and extracted with EtOAc (2×100 mL). The aqueous phase was washed once with EtOAc (50 mL). The organic solutions were combined, washed with water (100 mL) and brine (50 mL), and dried (Na2SO4). The crude material was filtered through a silica pad (20% EtOAc/hexanes) and concentrated to give clear oil (0.47 g, 90%). 1H NMR (CDCl3) δ 7.18 (d, J=2.4 Hz, 1H), 7.07 (d, J=8.7 Hz, 1H), 6.62 (d, J=8.7 Hz, 1H), 4.34-4.28 (m, 1H), 3.71-3.23 (m, 6H), 3.03-3.04 (m, 2H), 2.19-1.95 (m, 2H), 1.47 (s, 9H); ESI-MS (m/z, %): 423, 421 (M+Na, 8), 401, 399 (MH+, 2), 343, 345 (100).

Workup

  1. customwas kept at 0° C.
  2. stirringwas then stirred for 1 hour at 0° C
  3. stirringwas stirred for 1 hour at 0° C
  4. extractionextracted with EtOAc (2×100 mL)
  5. washThe aqueous phase was washed once with EtOAc (50 mL)
  6. washwashed with water (100 mL) and brine (50 mL)
  7. dry with materialdried (Na2SO4)
  8. filtrationThe crude material was filtered through a silica pad (20% EtOAc/hexanes)
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-150f1ee4cc4b4675bb0d3b0261673ff5
Source dataset
uspto-grants-2012_01
Patent number
US08106043B2

Reaction notes

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