1,4-Dioxane → tert-Butyl [2-(8-Methoxy-1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]carbamate

HRID 540123Notes

Reaction equation

HRID 540123 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9](OC(F)(F)F)[CH:10]=2)[N:5]=[C:4]([N:17]2[CH2:23][C:22]3[CH:24]=[CH:25][CH:26]=[CH:27][C:21]=3[S:20](=[O:29])(=[O:28])[CH2:19][CH2:18]2)[CH:3]=1.[C:30](=[O:37])([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])[NH2:31].C[C:39](C)([O-:41])C.[Na+].O1CCOC[CH2:45]1>C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].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]>[CH3:39][O:41][C:26]1[CH:25]=[CH:24][C:22]2[CH2:23][N:17]([C:4]3[CH:3]=[C:2]([NH:31][C:30](=[O:37])[O:32][C:33]([CH3:36])([CH3:35])[CH3:34])[C:11]4[C:6](=[CH:7][CH:8]=[C:9]([CH3:45])[CH:10]=4)[N:5]=3)[CH2:18][CH2:19][S:20](=[O:28])(=[O:29])[C:21]=2[CH:27]=1

Participants

7

Reactant 4

HCID 312751,4-DioxaneHCID 77922tert-Butyl carbamateHCID 23676156Sodium t-butoxideHCID 712545694-(4-Chloro-6-(trifluoromethoxy)quinolin-2-yl)-2,3,4,5-tetrahydro-1,4-benzothiazepine 1,1-dioxide

Product 1

HCID 71262340tert-Butyl [2-(8-Methoxy-1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]carbamate

Reagents, catalysts & solvents 2

HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst

Conditions

Temperature
120 °C

Procedure

A mixture solution of 4-(4-chloro-6-methylquinolin-2-yl)-8-methoxy-2,3,4,5-tetrahydro-1,4-benzothiazepine 1,1-dioxide (60.0 mg, 0.15 mmol, prepared in analogy to 4-(4-chloro-6-(trifluoromethoxy)quinolin-2-yl)-2,3,4,5-tetrahydro-1,4-benzothiazepine 1,1-dioxide in Example 17-1 by using 2,4-dichloro-6-methylquinoline and 8-methoxy-2,3,4,5-tetrahydro-1,4-benzothiazepine 1,2-dioxide), tert-butyl carbamate (45.0 mg, 0.37 mmol), 1,1′-bis(diphenylphosphino)ferrocene (11.2 mg, 0.02 mmol), 1,1′-bis(diphenylphosphino)ferrocenedichloropalladium(II) (15.0 mg, 0.02 mmol), and sodium tert-butoxide (75.0 mg, 0.72 mmol) in 1,4-dioxane (2.0 mL) was heated with stirring at 120° C. for 2 hours. After being cooled to room temperature, the reaction mixture was extracted with ethyl acetate (100 mL), washed with brine (50 mL×2), dried over anhydrous sodium sulfate and concentrated in vacuo to afford 59.9 mg of the crude product as yellow oil. MS obsd. (ESI+) [(M+H)+] 484.

Workup

  1. temperatureAfter being cooled to room temperature
  2. extractionthe reaction mixture was extracted with ethyl acetate (100 mL)
  3. washwashed with brine (50 mL×2)
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-8a772a97cfbe4087a3107eb02eb837c9
Source dataset
uspto-grants-2014_10
Patent number
US08871756B2

Reaction notes

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