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

HRID 571971Notes

Reaction equation

HRID 571971 reaction equation
C([O-])([O-])=O.[K+].[K+].[C@@H]1(N)CCCC[C@H]1N.[O:15]=[C:16]1[NH:21][CH2:20][CH:19]2[CH2:22][CH2:23][N:24]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:25][CH:18]2[O:17]1.I[C:34]1[CH:43]=[CH:42][C:37]2[O:38][CH2:39][CH2:40][O:41][C:36]=2[CH:35]=1>O1CCOCC1.[Cu]I>[O:38]1[CH2:39][CH2:40][O:41][C:36]2[CH:35]=[C:34]([N:21]3[CH2:20][CH:19]4[CH2:22][CH2:23][N:24]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:25][CH:18]4[O:17][C:16]3=[O:15])[CH:43]=[CH:42][C:37]1=2

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 438061,2-Diaminocyclohexane, trans-HCID 27761766-Iodo-2,3-dihydro-1,4-benzodioxineHCID 89602371rac-(4aR*,8aR*)-tert-butyl 2-oxohexahydro-2H-pyrido[4,3-e][1,3]oxazine-7(3H)-carboxylate

Product 1

HCID 117641627Rac-(4aR*,8aR*)-tert-butyl 3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-oxohexahydro-2H-pyrido[4,3-e][1,3]oxazine-7(3H)-carboxylateYield 62.4%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 312751,4-DioxaneSolvent

Procedure

A vial was charged with K2CO3 (0.22 g, 1.56 mmol, 2 eq.), CuI (0.01 g, 0.08 mmol, 0.1 eq.) and trans-1,2-cyclohexane diamine (0.01 g, 0.08 mmol, 0.1 eq.), rac-(4aR*,8aR*)-tert-butyl 2-oxohexahydro-2H-pyrido[4,3-e][1,3]oxazine-7(3H)-carboxylate (Preparation A, 0.2 g, 0.78 mmol) and flushed with nitrogen for 5 min. A solution of 6-iodo-2,3-dihydrobenzo[b][1,4]dioxine (0.21 g, 0.78 mmol, 1.01 eq.) in dry dioxane (0.78 mL) was added and the resulting suspension was at 110° C. for 40 h. The reaction mixture was cooled to rt and filtered over Celite. The solid was washed by EA (2×10 mL). The filtrate was concentrated to dryness and the residue was purified by CC (DCM/MeOH 49:1 to 19:1) to give the title compound as a beige foam (0.19 g).

Workup

  1. customflushed with nitrogen for 5 min
  2. filtrationfiltered over Celite
  3. washThe solid was washed by EA (2×10 mL)
  4. concentrationThe filtrate was concentrated to dryness
  5. customthe residue was purified by CC (DCM/MeOH 49:1 to 19:1)

Sources & evidence

ORD record
ord-9762e05723124d5fb2a9a2a82b2510b7
Source dataset
uspto-grants-2015_05
Patent number
US09029368B2

Reaction notes

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