Potassium Carbonate → Rac-(4aR*,8aR*)-tert-butyl 3-(4-(4-methoxybenzyl)-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)-2-oxohexahydro-2H-pyrido[4,3-e][1,3]oxazine-7(3H)-carboxylate

HRID 571972Notes

Reaction equation

HRID 571972 reaction equation
I[C:2]1[CH:21]=[CH:20][C:5]2S[CH2:7][C:8](=[O:19])[N:9]([CH2:10][C:11]3[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=3)[C:4]=2[CH:3]=1.[O:22]=[C:23]1[NH:28][CH2:27][CH:26]2[CH2:29][CH2:30][N:31]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:32][CH:25]2[O:24]1.C(=O)([O-])[O-:41].[K+].[K+].CN[C@@H]1CCCC[C@H]1NC>C(Cl)Cl.CO.[Cu]I.O1CCOCC1>[CH3:18][O:17][C:14]1[CH:15]=[CH:16][C:11]([CH2:10][N:9]2[C:8](=[O:19])[CH2:7][O:41][C:5]3[CH:20]=[CH:21][C:2]([N:28]4[CH2:27][CH:26]5[CH2:29][CH2:30][N:31]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:32][CH:25]5[O:24][C:23]4=[O:22])=[CH:3][C:4]2=3)=[CH:12][CH:13]=1

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 2733821trans-N,N'-dimethyl-1,2-cyclohexanediamineHCID 89602371rac-(4aR*,8aR*)-tert-butyl 2-oxohexahydro-2H-pyrido[4,3-e][1,3]oxazine-7(3H)-carboxylateHCID 896023986-iodo-4-(4-methoxybenzyl)-2H-benzo[b][1,4]thiazin-3(4H)-one

Product 1

HCID 117641643Rac-(4aR*,8aR*)-tert-butyl 3-(4-(4-methoxybenzyl)-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)-2-oxohexahydro-2H-pyrido[4,3-e][1,3]oxazine-7(3H)-carboxylateYield 58.9%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 312751,4-DioxaneSolventHCID 21226129Dichloromethane methanolSolvent

Conditions

Temperature
100 °C

Procedure

In a 7 mL sealed vial were introduced 6-iodo-4-(4-methoxybenzyl)-2H-benzo[b][1,4]thiazin-3(4H)-one (0.2 g, 0.486 mmol), rac-(4aR*,8aR*)-tert-butyl 2-oxohexahydro-2H-pyrido[4,3-e][1,3]oxazine-7(3H)-carboxylate (Preparation A, 0.15 g, 0.584 mmol, 1.2 eq.), potassium carbonate (0.134 g, 2 eq.), (R,R)-(−)-N,N′-dimethyl-1,2-cyclohexanediamine (0.01 g, 0.06 mmol, 0.1 eq.), CuI (0.11 g, 0.57 mmol, 1 eq.) and dioxane (2.3 mL). The suspension was stirred at 100° C. for 2 days. The mixture was cooled to rt, diluted with DCM/MeOH (9:1, 2 mL) and filtered. The yellow salt obtained was washed with DCM/MeOH (9:1, 2×10 mL). The combined filtrates were concentrated under reduced pressure. The residue was purified (DCM/MeOH 9:1) to afford the title compound as a greenish foam (0.15 g).

Workup

  1. customIn a 7 mL sealed vial
  2. temperatureThe mixture was cooled to rt
  3. filtrationfiltered
  4. customThe yellow salt obtained
  5. washwas washed with DCM/MeOH (9:1, 2×10 mL)
  6. concentrationThe combined filtrates were concentrated under reduced pressure
  7. customThe residue was purified (DCM/MeOH 9:1)

Sources & evidence

ORD record
ord-73798d41f70c48659614feb33ef4731b
Source dataset
uspto-grants-2015_05
Patent number
US09029368B2

Reaction notes

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