Acetic Acid → tert-Butyl 3-(2H-benzo[b][1,4]thiazin-4(3H)-yl)pyrrolidine-1-carboxylate

HRID 1917239Notes

Reaction equation

HRID 1917239 reaction equation
[S:1]1[CH2:6][CH2:5][NH:4][C:3]2[CH:7]=[CH:8][CH:9]=[CH:10][C:2]1=2.[C:11]([N:18]1[CH2:22][CH2:21][C:20](=O)[CH2:19]1)([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12].C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[S:1]1[CH2:6][CH2:5][N:4]([CH:21]2[CH2:20][CH2:19][N:18]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:22]2)[C:3]2[CH:7]=[CH:8][CH:9]=[CH:10][C:2]1=2

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 1510642,3-Dihydro-1,4-benzothiazineHCID 471360Tert-butyl 3-oxopyrrolidine-1-carboxylate2×HCID 5049666Sodium triacetoxyborohydride2×

Product 1

HCID 59144136tert-Butyl 3-(2H-benzo[b][1,4]thiazin-4(3H)-yl)pyrrolidine-1-carboxylateYield 19.4%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of 3,4-dihydro-2H-benzo[b][1,4]thiazine (1.00 g, 6.61 mmol), N-boc-3-pyrrolidinone (1.34 g, 7.27 mmol), and acetic acid (0.94 mL, 16.52 mmol) in 1,2-dichloroethane (20 mL) was cooled to 0° C. and then treated with solid sodium triacetoxyborohydride (2.10 g, 9.92 mmol). The reaction was brought to room temperature and was stirred for 11 hours. Additional equivalents of each of sodium triacetoxyborohydride (1.40 g, 6.61 mmol) and N-boc-3-pyrrolidinone (1.22 g, 6.61 mmol) were added to the reaction mixture. The reaction was stirred for 2 more days and was then quenched with 3 N NaOH (50 mL). The mixture was transferred to a separatory funnel and extracted with EtOAc (2×50 mL). The organic phase was washed with brine (50 mL) and dried (Na2SO4). The crude material was subject to flash chromatography on silica gel (10% EtOAc/hexanes then 20% EtOAc/hexanes). The sample was subject to additional flash chromatography on silica gel (7.5-15% EtOAc/hexanes) to give viscous oil (0.41 g, 19%). 1H NMR (CDCl3) δ 7.08 (dd, J=0.9, 7.5 Hz, 1H), 7.04-6.99 (m, 1H), 6.77 (d, J=8.1 Hz, 1H), 6.67-6.72 (m, 1H), 4.39-4.36 (m, 1H), 3.73-3.72 (m, 6H), 3.10-3.06 (m, 2H), 2.20-2.00 (m, 2H), 1.47 (s, 9H); ESI-MS (m/z, %): 345, 343 (M+Na, 4), 322, 320 (MH+, 3), 267, 265 (100).

Workup

  1. customwas brought to room temperature
  2. stirringThe reaction was stirred for 2 more days
  3. customwas then quenched with 3 N NaOH (50 mL)
  4. customThe mixture was transferred to a separatory funnel
  5. extractionextracted with EtOAc (2×50 mL)
  6. washThe organic phase was washed with brine (50 mL)
  7. dry with materialdried (Na2SO4)

Sources & evidence

ORD record
ord-66ef755136304f3a8b2845b484176c47
Source dataset
uspto-grants-2013_12
Patent number
US08618286B2

Reaction notes

Loading…