Borane → (S)-tert-Butyl-1-(2-(7-nitro-2H-benzo[b][1,4]thiazin-4(3H)-yl)ethyl)pyrrolidine-2-carboxylate

HRID 424528Notes

Reaction equation

HRID 424528 reaction equation
B.C1COCC1.[N+:7]([C:10]1[CH:11]=[CH:12][C:13]2[N:18]([C:19](=O)[CH2:20][N:21]3[CH2:25][CH2:24][CH2:23][C@H:22]3[C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:17][CH2:16][S:15][C:14]=2[CH:34]=1)([O-:9])=[O:8]>>[C:29]([O:28][C:26]([C@@H:22]1[CH2:23][CH2:24][CH2:25][N:21]1[CH2:20][CH2:19][N:18]1[CH2:17][CH2:16][S:15][C:14]2[CH:34]=[C:10]([N+:7]([O-:9])=[O:8])[CH:11]=[CH:12][C:13]1=2)=[O:27])([CH3:32])([CH3:30])[CH3:31]

Participants

4

Reactant 3

HCID 6331BoraneHCID 8028TetrahydrofuranHCID 59144152(S)-tert-Butyl-1-(2-(7-nitro-2H-benzo[b][1,4]thiazin-4(3H)-yl)-2-oxoethyl)pyrrolidine-2-carboxylate

Product 1

HCID 59144185(S)-tert-Butyl-1-(2-(7-nitro-2H-benzo[b][1,4]thiazin-4(3H)-yl)ethyl)pyrrolidine-2-carboxylate

Procedure

IM Borane in THF (17.18 mL, 17.18 mmol) was added to (S)-tert-butyl 1-(2-(7-nitro-2H-benzo[b][1,4]thiazin-4(3H)-yl)-2-oxoethyl)pyrrolidine-2-carboxylate (1.4 g, 3.44 mmol), and the resulting yellow solution was stirred at room temperature overnight (17 hours). The yellow solution was cooled to 0° C. and carefully quenched with MeOH (10 mL). The solution was concentrated, dissolved in MeOH (50 mL), and concentrated again to give a dark yellow residue. This residue was subjected to silica gel chromatography using the Biotage purification system (column: Silicycle 80 g; 20:80 EtOAc:hexanes gradient to 60:40 EtOAc:hexanes over 10 column volumes; flow rate=45 mL/min; collection wavelength: 254 nm). A yellow residue was obtained (550 mg, 40.7%). 1H-NMR (CDCl3) δ 7.96 (d, J=2.7 Hz, 1H), 7.87 (dd, J=2.7, 9.3 Hz, 1H), 6.68 (d, J=9.3 Hz, 1H), 3.86-3.82 (m, 2H), 3.57 (t, J=7.5 Hz, 2H), 3.24-3.10 (m, 2H), 3.05-2.96 (m, 3H), 2.75-2.63 (m, 1H), 2.52-2.41 (m, 1H), 2.15-2.04 (m, 1H), 1.97-1.78 (m, 3H), 1.44 (s, 9H); ESI-MS (m/z, %): 394 (MH+, 25), 338 (100).

Workup

  1. temperatureThe yellow solution was cooled to 0° C.
  2. customcarefully quenched with MeOH (10 mL)
  3. concentrationThe solution was concentrated
  4. dissolutiondissolved in MeOH (50 mL)
  5. concentrationconcentrated again
  6. customto give a dark yellow residue
  7. customthe Biotage purification system (column: Silicycle 80 g; 20:80 EtOAc:hexanes gradient to 60:40 EtOAc:hexanes over 10 column volumes; flow rate=45 mL/min; collection wavelength: 254 nm)
  8. customA yellow residue was obtained (550 mg, 40.7%)

Sources & evidence

ORD record
ord-a65345200e0f411c818906b227217b29
Source dataset
uspto-grants-2012_01
Patent number
US08106043B2

Reaction notes

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