Tetrahydrofuran → tert-butyl (2,3-dihydro-1,4-benzodioxin-6-ylmethyl)(1-(2-(5-(1-hydroxypropyl)-7-methoxy-2-oxoquinolin-1(2H)-yl)ethyl)piperidin-4-yl)carbamate

HRID 2193282Notes

Reaction equation

HRID 2193282 reaction equation
O1CC[CH2:3][CH2:2]1.[C:6]([O:10][C:11](=[O:47])[N:12]([CH2:36][C:37]1[CH:46]=[CH:45][C:40]2[O:41][CH2:42][CH2:43][O:44][C:39]=2[CH:38]=1)[CH:13]1[CH2:18][CH2:17][N:16]([CH2:19][CH2:20][N:21]2[C:30]3[C:25](=[C:26]([CH:33]=[O:34])[CH:27]=[C:28]([O:31][CH3:32])[CH:29]=3)[CH:24]=[CH:23][C:22]2=[O:35])[CH2:15][CH2:14]1)([CH3:9])([CH3:8])[CH3:7].C([Mg]Br)C.O1CCCC1.[Cl-].[NH4+]>C(Cl)(Cl)Cl.O>[C:6]([O:10][C:11](=[O:47])[N:12]([CH2:36][C:37]1[CH:46]=[CH:45][C:40]2[O:41][CH2:42][CH2:43][O:44][C:39]=2[CH:38]=1)[CH:13]1[CH2:14][CH2:15][N:16]([CH2:19][CH2:20][N:21]2[C:30]3[C:25](=[C:26]([CH:33]([OH:34])[CH2:2][CH3:3])[CH:27]=[C:28]([O:31][CH3:32])[CH:29]=3)[CH:24]=[CH:23][C:22]2=[O:35])[CH2:17][CH2:18]1)([CH3:9])([CH3:7])[CH3:8]

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 25517Ammonium ChlorideHCID 59398315tert-butyl(2,3-dihydro-1,4-benzodioxin-6-ylmethyl)(1-(2-(5-formyl-7-methoxy-2-oxoquinolin-1(2H)-yl)ethyl)piperidin-4-yl)carbamateHCID 178420660HCID 178420660, compound

Product 1

HCID 59398004tert-butyl (2,3-dihydro-1,4-benzodioxin-6-ylmethyl)(1-(2-(5-(1-hydroxypropyl)-7-methoxy-2-oxoquinolin-1(2H)-yl)ethyl)piperidin-4-yl)carbamate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6212ChloroformSolvent

Procedure

To 20 mL of a tetrahydrofuran solution containing 0.65 g of tert-butyl(2,3-dihydro-1,4-benzodioxin-6-ylmethyl)(1-(2-(5-formyl-7-methoxy-2-oxoquinolin-1(2H)-yl)ethyl)piperidin-4-yl)carbamate, 8.8 mL of 1 mol/L ethylmagnesium bromide/tetrahydrofuran was added at −78° C. and stirred for 1.5 hours. To the reaction mixture, aqueous saturated ammonium chloride solution, water and chloroform were added. The organic layer was separated, washed sequentially with aqueous saturated sodium hydrogen carbonate solution and aqueous saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The residue thus obtained was purified by silica gel column chromatography [Silica Gel; Kanto Chemical Co., Inc., Silica Gel 60N, eluent; chloroform:methanol=20:1], to give 200 mg of tert-butyl(2,3-dihydro-1,4-benzodioxin-6-ylmethyl)(1-(2-(5-(1-hydroxypropyl)-7-methoxy-2-oxoquinolin-1(2H)-yl)ethyl)piperidin-4-yl)carbamate as a yellow oil.

Workup

  1. additionwas added at −78° C.
  2. customThe organic layer was separated
  3. washwashed sequentially with aqueous saturated sodium hydrogen carbonate solution and aqueous saturated sodium chloride solution
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customthe solvent was removed under reduced pressure
  6. customThe residue thus obtained
  7. customwas purified by silica gel column chromatography [Silica Gel; Kanto Chemical Co., Inc., Silica Gel 60N, eluent; chloroform:methanol=20:1]

Sources & evidence

ORD record
ord-e36e308eb1394392a18a2d5bea36b491
Source dataset
uspto-grants-2012_12
Patent number
US08329694B2

Reaction notes

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