Sodium borohydride → 5-[1-(2-Chlorophenyl)-7-ethoxycarbonyl-7-methyloctyl]-4,5,6,7-tetrahydropyrrolo[3,2-c]pyridine-1-carboxylic acid tert-butyl ester

HRID 1801535Notes

Reaction equation

HRID 1801535 reaction equation
[BH4-].[Na+].[Br-].[C:4]([O:8][C:9]([N:11]1[C:19]2[CH:18]=[CH:17][N+:16]([CH:20]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=3[Cl:35])[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH:26]([CH3:28])[CH3:27])=[CH:15][C:14]=2[CH:13]=[CH:12]1)=[O:10])([CH3:7])([CH3:6])[CH3:5]>CCO>[C:4]([O:8][C:9]([N:11]1[C:19]2[CH2:18][CH2:17][N:16]([CH:20]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=3[Cl:35])[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][C:26]([C:9]([O:8][CH2:4][CH3:5])=[O:10])([CH3:28])[CH3:27])[CH2:15][C:14]=2[CH:13]=[CH:12]1)=[O:10])([CH3:6])([CH3:7])[CH3:5]

Participants

4

Reactant 2

HCID 4311764Sodium borohydrideHCID 675180631-tert-butoxycarbonyl-5-[1-(2-chlorophenyl)-7-methyloctyl]-1H-pyrrolo[3,2-c]pyridin-5-ium bromide

Product 1

HCID 675178445-[1-(2-Chlorophenyl)-7-ethoxycarbonyl-7-methyloctyl]-4,5,6,7-tetrahydropyrrolo[3,2-c]pyridine-1-carboxylic acid tert-butyl esterYield 93.3%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Portions of sodium borohydride (0.16 g, 4.28 mmol) were added to a solution of 1-tert-butoxycarbonyl-5-[1-(2-chlorophenyl)-7-methyloctyl]-1H-pyrrolo[3,2-c]pyridin-5-ium bromide (1.3 g, 2.14 mmol) in 70% EtOH (30 mL) at room temperature over 30 minutes. Once the addition was complete, the mixture was stirred for 0.5 hours. The solvent was evaporated under reduced pressure and water (60 mL) was added. The product was extracted with dichloromethane (3×80 mL). The combined organic extracts were dried over sodium sulfate, filtered, and concentrated. The resultant tertiary amine was purified by column chromatography (silica gel, ethyl acetate/heptane=1/10 to 1/3) to yield 5-[1-(2-chlorophenyl)-7-ethoxycarbonyl-7-methyloctyl]-4,5,6,7-tetrahydropyrrolo[3,2-c]pyridine-1-carboxylic acid tert-butyl ester (0.53 g, 46.9%) as a yellow oil. 1H NMR (Field: 300 MHz, Solvent: CD3OD/TMS) δ (ppm): 7.52 (d, 1H, J=7.8 Hz), 7.37 (d, 1H, J=7.8 Hz), 7.27 (t, 1H, J=6.6 Hz), 7.19 (t, 1H, J=7.5 Hz), 7.12 (d, 1H, J=3.3 Hz), 5.95 (d, 1H, J=3.3 Hz), 4.16-4.13 (m, 1H), 4.09 (q, 2H, J=7.2 Hz), 3.31 (d, 1H, J=13.8 Hz), 2.85-2.59 (m, 4H), 1.95-1.76 (m, 2H), 1.55 (s, 9H), 1.45-1.40 (m, 2H), 1.28-1.14 (m, 6H), 1.21 (t, 3H, J=7.2 Hz), 1.11 (s, 6H). 13C NMR (Field: 75 MHz, Solvent: CDCl3/TMS) δ (ppm): 178.00, 149.47, 139.70, 134.90, 129.45, 129.15, 127.89, 127.60, 126.80, 120.94, 119.76, 109.18, 83.24, 63.80, 60.30, 48.78, 42.32, 40.88, 33.20, 30.56, 28.31, 26.45, 25.44, 25.38, 25.03, 14.52. HRMS (FIR): Calculated for C30H43ClN2O2 (M+H)+: 531.2990, found 531.2933.

Workup

  1. additionOnce the addition
  2. customThe solvent was evaporated under reduced pressure and water (60 mL)
  3. additionwas added
  4. extractionThe product was extracted with dichloromethane (3×80 mL)
  5. dry with materialThe combined organic extracts were dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe resultant tertiary amine was purified by column chromatography (silica gel, ethyl acetate/heptane=1/10 to 1/3)

Sources & evidence

ORD record
ord-b72ff2f3aef2467cbf0a2f05a073df47
Source dataset
uspto-grants-2013_01
Patent number
US08349833B2

Reaction notes

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