Sodium borohydride → HCID 42602278, compound

HRID 1867644Notes

Reaction equation

HRID 1867644 reaction equation
[F:1][C:2]([F:30])([F:29])[C:3]1[CH:4]=[C:5]([CH:22]=[C:23]([C:25]([F:28])([F:27])[F:26])[CH:24]=1)[CH2:6][O:7][CH2:8][C:9]1([CH2:18][CH2:19][C:20]#[N:21])[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[CH2:11][O:10]1.[BH4-].[Na+]>CO.O.O.O.O.O.O.[Ni](Cl)Cl>[F:27][C:25]([F:26])([F:28])[C:23]1[CH:22]=[C:5]([CH:4]=[C:3]([C:2]([F:30])([F:29])[F:1])[CH:24]=1)[CH2:6][O:7][CH2:8][C:9]1([CH2:18][CH2:19][CH2:20][NH2:21])[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[CH2:11][O:10]1

Participants

5

Reactant 2

HCID 4311764Sodium borohydrideHCID 86630223HCID 86630223, compound

Product 1

HCID 42602278HCID 42602278, compound

Reagents, catalysts & solvents 2

HCID 11791229Dichloronickel;hexahydrateCatalystHCID 887MethanolSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 3-(1-((3,5-bis(trifluoromethyl)benzyloxy)methyl)-1,3-dihydroisobenzofuran-1-yl)propanenitrile (190 mg, 0.44 mmol) and nickel(II) chloride hexahydrate (158 mg, 0.66 mmol) in methanol (4 mL) at 0° C. was added sodium borohydride (117 mg, 3.1 mmol) in several portions over 30 minutes. The ice bath was removed and stirring continued for 1 h. Very clean and mostly complete conversion to product (by LC/MS) was observed. The reaction was cooled to 0° C. and treated with concentrated hydrochloric acid (85 μL). After 5 min, celite was added, and the mixture was filtered. The solution was made basic by addition of solid sodium bicarbonate, and filtered again. The organics were concentrated to give the crude amine which was purified by column chromatography (10% MeOH/DCM-->10:90:0.5 MeOH/DCM/Me3N in EtOH) to give 114 mg (59%) as a colorless oil. 1H-NMR (CDCl3, 300 MHz) δ 7.73 (s, 1H), 7.63 (s, 2H), 7.05-7.40 (m, 4H), 5.11 (s, 2H), 4.61 (qAB, JAB=13.1 Hz, 2H), 3.66 (s, 2H), 2.64 (m, 2H), 1.70-2.10 (m, 4H), 1.50 (m, 1H), 1.20 (m, 1H); 13C-NMR (CDCl3, 126 MHz) δ 141.42, 141.39, 140.1, 131.7 (q, J=33.6 Hz), 128.1, 127.5, 127.1, 123.4 (q, J=273 Hz), 121.6, 121.4, 121.1, 90.3, 76.8, 72.9, 72.0, 42.3, 34.1, 27.3. Mass spec.: 434.25 (MH)+. Accurate mass spec.: m/z 434.1542 [MH]+, Δ=1.3 ppm.

Workup

  1. customThe ice bath was removed
  2. additiontreated with concentrated hydrochloric acid (85 μL)
  3. waitAfter 5 min
  4. additioncelite was added
  5. filtrationthe mixture was filtered
  6. additionThe solution was made basic by addition of solid sodium bicarbonate
  7. filtrationfiltered again
  8. concentrationThe organics were concentrated

Sources & evidence

ORD record
ord-2d5f9add0591460188a4dd28e31b2ac6
Source dataset
uspto-grants-2009_12
Patent number
US07632861B2

Reaction notes

Loading…