Diethyl Ether → 3-(2-{2-[2-(2-Dimethylamino-ethoxy)-naphthalen-1-yl]-ethoxy}-benzenesulfonylamino)-4-oxo-butyric acid tert-butyl ester

HRID 1814340Notes

Reaction equation

HRID 1814340 reaction equation
[C:1]([O:5][C:6](=[O:44])[CH2:7][CH:8]([NH:15][S:16]([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=1[O:25][CH2:26][CH2:27][C:28]1[C:37]2[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=2)[CH:31]=[CH:30][C:29]=1[O:38][CH2:39][CH2:40][N:41]([CH3:43])[CH3:42])(=[O:18])=[O:17])[C:9](N(OC)C)=[O:10])([CH3:4])([CH3:3])[CH3:2].C1COCC1.CCOCC.[H-].[H-].[H-].[H-].[Li+].[Al+3]>CO.C(Cl)Cl.C(Cl)Cl.C(#N)C>[C:1]([O:5][C:6](=[O:44])[CH2:7][CH:8]([NH:15][S:16]([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=1[O:25][CH2:26][CH2:27][C:28]1[C:37]2[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=2)[CH:31]=[CH:30][C:29]=1[O:38][CH2:39][CH2:40][N:41]([CH3:43])[CH3:42])(=[O:18])=[O:17])[CH:9]=[O:10])([CH3:2])([CH3:4])[CH3:3]

Participants

8

Reactant 4

HCID 3283Diethyl EtherHCID 8028TetrahydrofuranHCID 21226445Aluminium lithium hydrideHCID 86588232HCID 86588232, compound

Product 1

HCID 865882333-(2-{2-[2-(2-Dimethylamino-ethoxy)-naphthalen-1-yl]-ethoxy}-benzenesulfonylamino)-4-oxo-butyric acid tert-butyl esterYield 97%

Reagents, catalysts & solvents 3

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolventHCID 21226129Dichloromethane methanolSolvent

Conditions

Temperature
-65 °C

Procedure

3-(2-{2-[2-(2-Dimethylamino-ethoxy)-naphthalen-1-yl]-ethoxy}-benzenesulfonylamino)-N-methoxy-N-methyl-succinamic acid tert-butyl ester (230 mg, 0.366 mmol) was dissloved in a mixture of freshly distilled THF (0.85 mL) and ether (1.35 mL). The mix was chilled to −65° C. in a dry-ice/chlorofrom bath. LiAlH4 solution (1.23 mL of 1.0 M solution in ether, 1.23 mmol) was added via syringe. The reaction became heterogeneous. Acetonitrile (0.2 mL) and CH2Cl2 (0.2 mL) were added to aid dissolution. The reaction was stirred at −65° C. for 1.25 hours. TLC analysis (5% MeOH/CH2Cl2, silca) indicated the reaction was complete. The reaction was carefully quenched with saturated aqueous KHSO4 (2 mL) and was allowed to warm to room temperature. The reaction was diluted with saturated aqueous NaHCO3 and was extracted three times with EtOAc. The organic extracts were combined, dried over Na2SO4, decanted, and concentrated to give 3-(2-{2-[2-(2-dimethylamino-ethoxy)-naphthalen-1-yl]-ethoxy}-benzenesulfonylamino)-4-oxo-butyric acid tert-butyl ester (202 mg, 0.35 mmol) in 97% yield. MS (APCI) m/z 571.1 (M+1).

Workup

  1. customThe reaction was carefully quenched with saturated aqueous KHSO4 (2 mL)
  2. temperatureto warm to room temperature
  3. additionThe reaction was diluted with saturated aqueous NaHCO3
  4. extractionwas extracted three times with EtOAc
  5. dry with materialdried over Na2SO4
  6. customdecanted
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-67e2a412900c4fd9829f6980e7112d8a
Source dataset
uspto-grants-2005_04
Patent number
US06875765B2

Reaction notes

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