Formaldehyde → 4-(2-Fluoro-4-nitro-phenoxy)-6-methoxy-7-(2-methyl-octahydro-cyclopenta[c]pyrrol-5-ylmethoxy)-quinoline

HRID 1924124Notes

Reaction equation

HRID 1924124 reaction equation
[F:1][C:2]1[CH:30]=[C:29]([N+:31]([O-:33])=[O:32])[CH:28]=[CH:27][C:3]=1[O:4][C:5]1[C:14]2[C:9](=[CH:10][C:11]([O:17][CH2:18][CH:19]3[CH2:26][CH:22]4[CH2:23][NH:24][CH2:25][CH:21]4[CH2:20]3)=[C:12]([O:15][CH3:16])[CH:13]=2)[N:8]=[CH:7][CH:6]=1.[C:34](#N)C.O.C=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>O>[F:1][C:2]1[CH:30]=[C:29]([N+:31]([O-:33])=[O:32])[CH:28]=[CH:27][C:3]=1[O:4][C:5]1[C:14]2[C:9](=[CH:10][C:11]([O:17][CH2:18][CH:19]3[CH2:26][CH:22]4[CH2:23][N:24]([CH3:34])[CH2:25][CH:21]4[CH2:20]3)=[C:12]([O:15][CH3:16])[CH:13]=2)[N:8]=[CH:7][CH:6]=1

Participants

6

Reactant 4

HCID 712FormaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 18373917Acetonitrile--water (1/1)HCID 578101424-(2-Fluoro-4-nitro-phenoxy)-6-methoxy-7-(octahydro-cyclopenta[c]pyrrol-5-ylmethoxy)-quinoline

Product 1

HCID 578102834-(2-Fluoro-4-nitro-phenoxy)-6-methoxy-7-(2-methyl-octahydro-cyclopenta[c]pyrrol-5-ylmethoxy)-quinolineYield 50%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
0 °C

Procedure

To a round bottom flask equipped with a magnetic stir bar was added 4-(2-Fluoro-4-nitro-phenoxy)-6-methoxy-7-(octahydro-cyclopenta[c]pyrrol-5-ylmethoxy)-quinoline (2.1 g, 3.9 mmol, 1.0 eq.) and acetonitrile/water 1:1 (5 ml, 5 ml). The reaction mixture was then cooled to 0° C. and 37% solution of formaldehyde in water was added (0.2 g, 7.8 mmol, 2.0 eq). While keeping the temperature at 0° C. Na(OAc)3BH was added (4.4 g, 20.7 mmol, 3.0 eq). After 1 hour the pH was adjusted to 10 and the aqueous was extracted 2× DCM (100 ml). Removal of the DCM resulted in a white solid. The compound was further purified with a biotage system using an eluent EtOAc and 5% MeOH, affording 4-(2-Fluoro-4-nitro-phenoxy)-6-methoxy-7-(2-methyl-octahydrocyclopenta-[c]pyrrol-5-ylmethoxy)-quinoline (0.9 g, 50% yield).). 1H NMR (400 MHz, CDCl3): 8.57 (d, 1H), 8.14 (dd, 1H), 8.12 (dd, 1H), 7.41 (s, 2H), 7.34 (t, 1H), 6.54 (d, 1H), 4.19 (d, 2H), 4.01 (s, 3H), 2.61 (m, 4H), 2.43 (m, 1H), 2.33 (s, 3H), 2.11 (m, 4H), 1.32 (m, 2H); MS (EI) for C25H26FN3O5: 468 (M+H+).

Workup

  1. customTo a round bottom flask equipped with a magnetic stir bar
  2. customat 0° C
  3. extractionthe aqueous was extracted 2× DCM (100 ml)
  4. customRemoval of the DCM
  5. customresulted in a white solid
  6. customThe compound was further purified with a biotage system

Sources & evidence

ORD record
ord-3d6c9c5a904c43a2a8bd7431dffef617
Source dataset
uspto-grants-2012_05
Patent number
US08178532B2

Reaction notes

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