Acetic Acid → tert-Butyl 2,2-dimethyl-5-((5-octylisoindolin-2-yl)methyl)-1,3-dioxan-5-ylcarbamate

HRID 710284Notes

Reaction equation

HRID 710284 reaction equation
Cl.[CH2:2]([C:10]1[CH:11]=[C:12]2[C:16](=[CH:17][CH:18]=1)[CH2:15][NH:14][CH2:13]2)[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH3:9].[CH:19]([C:21]1([NH:29][C:30](=[O:36])[O:31][C:32]([CH3:35])([CH3:34])[CH3:33])[CH2:26][O:25][C:24]([CH3:28])([CH3:27])[O:23][CH2:22]1)=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].CCN(CC)CC.CC(O)=O>ClCCCl>[CH3:27][C:24]1([CH3:28])[O:23][CH2:22][C:21]([NH:29][C:30](=[O:36])[O:31][C:32]([CH3:35])([CH3:34])[CH3:33])([CH2:19][N:14]2[CH2:13][C:12]3[C:16](=[CH:17][CH:18]=[C:10]([CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH3:9])[CH:11]=3)[CH2:15]2)[CH2:26][O:25]1

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 8471TriethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 24754730Tert-butyl (5-formyl-2,2-dimethyl-1,3-dioxan-5-yl)carbamateHCID 667265875-n-Octylisoindoline hydrochloride salt

Product 1

HCID 66726792tert-Butyl 2,2-dimethyl-5-((5-octylisoindolin-2-yl)methyl)-1,3-dioxan-5-ylcarbamateYield 94%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To a mixture of the product of Step E (0.03 g; 0.112 mmol), tert-butyl 5-formyl-2,2-dimethyl-1,3-dioxan-5-ylcarbamate (0.037 g; 0.115 mmol) and NaBH(OAc)3 (0.035 g; 0.17 mmol) in 1,2 dichloroethane (3 ml), Et3N (0.016 ml; 0.112 mmol) was added at room temperature, followed by AcOH (0.064 ml; 0.112 mmol). The resulting mixture was stirred overnight under N2. After dilution to 10 ml with Et2O, the mixture was washed with 1.M NaOH (2×2 ml), brine and dried over anhydrous MgSO4 and filtered. The filtrate was evaporated to dryness under reduced pressure. The residue was purified by FCC (SiO2; hexane/EtOAc 8:2) to give pure title compound (0.05 g; 92%) as colourless solid. 1H-NMR (CDCl3) 0.86 (tr, 3H, J=7 Hz); 1.25 (m, 10H); 1.41 (s, 3H); 1.44 (s, 9H); 1.47 (s, 3H); 1.57 (m, 2H); 2.56 (tr, 2H, J=7.92 Hz); 3.18 (s, 2H): 3.79 (d, 2H, J=11.7 Hz); 4.05 (s, 4H); 4.14 (d, 2H, J=11.7 Hz); 5.03 (s, 1H); 6.98 (s, 1H); 6.99 (d, 1H, J=8.14 Hz); 7.06 (d, 1H, J=8.14 Hz).

Workup

  1. additionwas added at room temperature
  2. washAfter dilution to 10 ml with Et2O, the mixture was washed with 1.M NaOH (2×2 ml), brine
  3. dry with materialdried over anhydrous MgSO4
  4. filtrationfiltered
  5. customThe filtrate was evaporated to dryness under reduced pressure
  6. customThe residue was purified by FCC (SiO2; hexane/EtOAc 8:2)

Sources & evidence

ORD record
ord-7aa926fa9431463dbb36e85690178c4f
Source dataset
uspto-grants-2015_11
Patent number
US09181182B2

Reaction notes

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