1,4-Dioxane → tert-Butyl {trans-1-[6-methyl-2-(1-oxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinolin-4-yl]-4-hydroxypyrrolidin-3-yl}carboxylate

HRID 540120Notes

Reaction equation

HRID 540120 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([CH3:12])[CH:10]=2)[N:5]=[C:4]([N:13]2[CH2:19][C:18]3[CH:20]=[CH:21][CH:22]=[CH:23][C:17]=3[S:16](=[O:24])[CH2:15][CH2:14]2)[CH:3]=1.[OH:25][C@@H:26]1[CH2:30][NH:29][CH2:28][C@H:27]1NC(=O)OC(C)(C)C.C1(P(C2CCCCC2)C2(N(C)C)CC=CC=C2C2C=CC=CC=2)CCCCC1.[CH3:67][C:68]([CH3:71])([O-:70])[CH3:69].[Na+].[O:73]1CCOC[CH2:74]1>>[CH3:12][C:9]1[CH:10]=[C:11]2[C:6](=[CH:7][CH:8]=1)[N:5]=[C:4]([N:13]1[CH2:19][C:18]3[CH:20]=[CH:21][CH:22]=[CH:23][C:17]=3[S:16](=[O:24])[CH2:15][CH2:14]1)[CH:3]=[C:2]2[N:29]1[CH2:30][C@@H:26]([OH:25])[C@H:27]([C:74]([O:70][C:68]([CH3:71])([CH3:69])[CH3:67])=[O:73])[CH2:28]1

Participants

6

Reactant 5

HCID 312751,4-DioxaneHCID 23676156Sodium t-butoxideHCID 59640689(3R,4R)-(4-Hydroxy-pyrrolidin-3-yl)-carbamic acid tert-butyl esterHCID 665453382-Dicyclohexylphosphino-2-(N,N-Dimethylamino)BiphenylHCID 712553794-(4-Chloro-6-methylquinolin-2-yl)-2,3,4,5-tetrahydro-1,4-benzothiazepine 1-oxide

Product 1

HCID 86691386tert-Butyl {trans-1-[6-methyl-2-(1-oxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinolin-4-yl]-4-hydroxypyrrolidin-3-yl}carboxylateYield 80%

Conditions

Temperature
120 °C

Procedure

A mixture of 4-(4-chloro-6-methylquinolin-2-yl)-2,3,4,5-tetrahydro-1,4-benzothiazepine 1-oxide (200 mg, 0.56 mmol, prepared in analogy to the one in Example 18-1), tert-butyl [trans-4-hydroxypyrrolidin-3-yl]carbamate (125 mg, 0.62 mmol), tris(2-benzylidene acetone) palladium(II) (50 mg, 0.055 mmol), 2-dicyclohexylphosphino-2-(N,N-dimethylamino)biphenyl (30 mg, 0.076 mmol), sodium tert-butoxide (60 mg, 0.625 mmol) and 1,4-dioxane (3 mL) in a 2-5 mL of process vial was heated at 120° C. under microwave irradiation for 2 hours. After being cooled to room temperature, the mixture was filtered and washed with ethyl acetate. The filtrate was washed with brine, dried over sodium sulfate, and concentrated in vacuo. The residue was purified by flash column chromatography (eluting with 10% methanol in dichloromethane) to afford 230 mg of the product as a white solid (yield was 80%).

Workup

  1. temperatureAfter being cooled to room temperature
  2. filtrationthe mixture was filtered
  3. washwashed with ethyl acetate
  4. washThe filtrate was washed with brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash column chromatography (eluting with 10% methanol in dichloromethane)

Sources & evidence

ORD record
ord-b5bd67c5874545aca5c20a92c6c2eff9
Source dataset
uspto-grants-2014_10
Patent number
US08871756B2

Reaction notes

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