Sodium triacetoxyborohydride → 8-(2-(4-Methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)ethyl)-2-(4-methyl-5-oxo-2,5-dihydrofuran-3-yl)-2,8-diazaspiro[4.5]decan-1-one

HRID 1501842Notes

Reaction equation

HRID 1501842 reaction equation
[CH3:1][C:2]1[C:10]2[CH2:9][O:8][C:7](=[O:11])[C:6]=2[CH:5]=[CH:4][C:3]=1[CH2:12][CH:13]=O.[CH3:15][C:16]1[C:20](=[O:21])[O:19][CH2:18][C:17]=1[N:22]1[CH2:26][CH2:25][C:24]2([CH2:31][CH2:30][NH:29][CH2:28][CH2:27]2)[C:23]1=[O:32].[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>C1COCC1>[CH3:1][C:2]1[C:3]([CH2:12][CH2:13][N:29]2[CH2:30][CH2:31][C:24]3([C:23](=[O:32])[N:22]([C:17]4[CH2:18][O:19][C:20](=[O:21])[C:16]=4[CH3:15])[CH2:26][CH2:25]3)[CH2:27][CH2:28]2)=[CH:4][CH:5]=[C:6]2[C:10]=1[CH2:9][O:8][C:7]2=[O:11]

Participants

5

Reactant 3

HCID 5049666Sodium triacetoxyborohydrideHCID 772312602-(4-Methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)acetaldehydeHCID 867095242-(4-Methyl-5-oxo-2,5-dihydrofuran-3-yl)-2,8-diazaspiro[4.5]decan-1-one

Product 1

HCID 727252688-(2-(4-Methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)ethyl)-2-(4-methyl-5-oxo-2,5-dihydrofuran-3-yl)-2,8-diazaspiro[4.5]decan-1-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of (4-Methyl-1-oxo-1,3-dihydro-2-benzofuran-5-yl)acetaldehyde (I-3) (100 mg, crude) and 2-(4-methyl-5-oxo-2,5-dihydrofuran-3-yl)-2,8-diazaspiro[4.5]decan-1-one (I-16) (145 mg, 0.58 mmol) in THF (5 mL) was stirred at rt for 2 hours and then NaBH(OAc)3 (167 mg, 0.79 mmol) was added to the mixture, which was further stirred at 50° C. for 3 hours. After quenching with saturated NH4Cl aq, the mixture was extracted with EtOAc and organic layer was dried over Na2SO4. Solvent was removed under reduced pressure and the residue was purified by prep-TLC (EtOAc/MeOH: 1/1) and prep-HPLC to give the title product. MS (ESI) m/z: 425 (M+H+); 1H NMR (400 MHz, MeOD): δ 7.69 (d, J=7.6 Hz, 1H), 7.50 (d, J=7.6 Hz, 1H), 5.38 (s, 2H), 5.27-5.25 (m, 2H), 4.20-4.14 (m, 2H), 3.83-3.80 (m, 1H), 3.68-3.66 (m, 1H), 3.42-3.38 (m, 2H), 3.33-3.23 (m, 4H), 2.41 (s, 3H), 2.39-2.30 (m, 2H), 2.24-2.17 (m, 2H), 2.10-2.03 (m, 5H).

Workup

  1. stirringwas further stirred at 50° C. for 3 hours
  2. customAfter quenching with saturated NH4Cl aq
  3. extractionthe mixture was extracted with EtOAc and organic layer
  4. dry with materialwas dried over Na2SO4
  5. customSolvent was removed under reduced pressure
  6. customthe residue was purified by prep-TLC (EtOAc/MeOH: 1/1)

Sources & evidence

ORD record
ord-84b2fa804e6c4663addea7607893d08a
Source dataset
uspto-grants-2015_12
Patent number
US09206198B2

Reaction notes

Loading…