Potassium Carbonate → tert-butyl 7-[2-(acetylamino)-1,3-thiazol-5-yl]-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylate

HRID 241092

Reaction equation

HRID 241092 reaction equation
Br[C:2]1[S:6][C:5]([NH:7][C:8](=[O:10])[CH3:9])=[N:4][CH:3]=1.[CH3:11][C:12]([O:15][C:16]([N:18]1[CH2:24][C:23]2[CH:25]=[C:26](B(O)O)[CH:27]=[CH:28][C:22]=2[O:21][CH2:20][CH2:19]1)=[O:17])([CH3:14])[CH3:13].C(=O)([O-])[O-].[K+].[K+].O1CCOCC1>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O>[C:8]([NH:7][C:5]1[S:6][C:2]([C:26]2[CH:27]=[CH:28][C:22]3[O:21][CH2:20][CH2:19][N:18]([C:16]([O:15][C:12]([CH3:13])([CH3:11])[CH3:14])=[O:17])[CH2:24][C:23]=3[CH:25]=2)=[CH:3][N:4]=1)(=[O:10])[CH3:9]

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 3502602-Acetamido-5-bromo-1,3-thiazoleHCID 59604707(4-(Tert-butoxycarbonyl)-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepin-7-yl)boronic acid

Product 1

HCID 59604271tert-butyl 7-[2-(acetylamino)-1,3-thiazol-5-yl]-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylateYield 56.5%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolvent

Conditions

Temperature
95 °C

Procedure

A mixture of N-(5-bromo-1,3-thiazol-2-yl)acetamide (1.00 g, 4.5 mmol), (4-{[(1,1-dimethylethyl)oxy]carbonyl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)boronic acid (example 1, step 2) (1.59 g, 5.4 mmol), potassium carbonate (2.50 g, 18 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (0.33 g, 0.45 mmol), 1,4-dioxane (20 mL), and water (2 mL) was degassed with nitrogen for 2 min, and then stirred at 95° C. for 16 h. The reaction mixture was cooled, diluted with ethyl acetate (100 mL), and filtered through celite. The filtrate was washed with brine (2×30 mL), dried over sodium sulfate, and concentrated. Column chromatography on silica (gradient 20-85% ethyl acetate in hexane) gave 1,1-dimethylethyl 7-[2-(acetylamino)-1,3-thiazol-5-yl]-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylate (0.99 g, 56% yield). MS (EI) for C19H23N3O4: 390 (MH+).

Workup

  1. customwas degassed with nitrogen for 2 min
  2. temperatureThe reaction mixture was cooled
  3. additiondiluted with ethyl acetate (100 mL)
  4. filtrationfiltered through celite
  5. washThe filtrate was washed with brine (2×30 mL)
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-93024e6fa0c647ea9873471e88603503
Source dataset
uspto-grants-2014_02
Patent number
US08648066B2

Linked notes

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