Sodium cyanoborohydride → 4-(1,3-Diacetoxypropan-2-yloxy)indoline

HRID 16573Notes

Reaction equation

HRID 16573 reaction equation
[BH3-]C#N.[Na+].[C:5]([O:8][CH2:9][CH:10]([O:16][C:17]1[CH:25]=[CH:24][CH:23]=[C:22]2[C:18]=1[CH:19]=[CH:20][NH:21]2)[CH2:11][O:12][C:13](=[O:15])[CH3:14])(=[O:7])[CH3:6]>C(O)(=O)C>[C:13]([O:12][CH2:11][CH:10]([O:16][C:17]1[CH:25]=[CH:24][CH:23]=[C:22]2[C:18]=1[CH2:19][CH2:20][NH:21]2)[CH2:9][O:8][C:5](=[O:7])[CH3:6])(=[O:15])[CH3:14]

Participants

4

Reactant 2

HCID 5003444Sodium cyanoborohydrideHCID 59343713HCID 59343713, compound

Product 1

HCID 686187354-(1,3-Diacetoxypropan-2-yloxy)indolineYield 100.2%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

NaBH3CN (0.94 g, 15 mmol) was added portionwise to a solution of 24 (1.46 g, 5 mmol) in acetic acid (40 mL) and the mixture was stirred at room temperature for 1 h. The solvent was evaporated and the residue was diluted with water, neutralised with NaHCO3 and extracted with EtOAc. The combined organic phases were washed with brine, dried and evaporated to give crude 4-(1,3-diacetoxypropan-2-yloxy)indoline (1.47 g, 100%) as a viscous oil: 1H NMR (90 MHz) δ 6.95 (t, J=7.2 Hz 1H), 6.24-6.68 (m, 2H), 4.62 (quintet, J=5.4 Hz, 1H), 4.20-4.46 (m, 4H), 3.64 (s, 1H), 4.52 (t, J=7.2 Hz, 2H), 2.94 (t, J=7.2 Hz, 2H), 2.06 (s, 6H). Without further purification, this material was dissolved in dry MeCN (40 mL) and treated with 4-azidobutyric acid (0.78 g, 6 mmol), followed by 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (1.34 g, 7 mmol) and the mixture was stirred at room temperature overnight. The solvent was evaporated and the residue was taken up in EtOAc (50 mL) washed with dilute aq. HCl, saturated aq. NaHCO3 and brine, dried and evaporated. Flash chromatography [EtOAc-hexanes (2:3)] gave 25 (1.33 g, 64%) as white crystals, mp 61-63° C. (Et2O-hexanes); 1H NMR (500 MHz) δ 7.87 (d, J=8.2 Hz, 1H), 7.16 (t, J=8.2 Hz, 1H), 6.68 (d, J=8.2 Hz, 1H), 4.70 (quintet, J=5.3 Hz, 1H), 4.34 (dd, J=11.9, 5.7 Hz, 2H), 4.29 (dd, J=11.9, 4.8 Hz, 2H), 4.07 (t, J=8.5 Hz, 2H), 3.45 (t, J=6.4 Hz, 2H), 3.12 (t, J=8.4 Hz, 2H), 2.51 (t, J=6.9 Hz, 2H), 2.06 (s, 6H), 2.03 (quintet, J=6.6 Hz, 2H). Anal. Calcd for C19H24N4O6: C, 56.43; H, 5.98; N, 13.85. Found: C, 56.23; H, 5.98; N, 13.61.

Workup

  1. customThe solvent was evaporated
  2. additionthe residue was diluted with water
  3. extractionextracted with EtOAc
  4. washThe combined organic phases were washed with brine
  5. customdried
  6. customevaporated

Sources & evidence

ORD record
ord-99af50762df4435dac1d2252dd032267
Source dataset
uspto-grants-2010_06
Patent number
US07737169B2

Reaction notes

Loading…