Lithium borohydride → 4-(3,3''-dimethyl-3',4',5',6'-tetrahydro-2'H-[2,2'; 6',2'']terpyridin-1'-ylmethyl)-3-hydroxymethyl-benzonitrile

HRID 1987352Notes

Reaction equation

HRID 1987352 reaction equation
C[O:2][C:3](=O)[C:4]1[CH:9]=[C:8]([C:10]#[N:11])[CH:7]=[CH:6][C:5]=1[CH2:12][N:13]1[CH:18]([C:19]2[C:24]([CH3:25])=[CH:23][CH:22]=[CH:21][N:20]=2)[CH2:17][CH2:16][CH2:15][CH:14]1[C:26]1[C:31]([CH3:32])=[CH:30][CH:29]=[CH:28][N:27]=1.[Li+].[BH4-]>C1COCC1.CO.[OH-].[Na+]>[CH3:25][C:24]1[C:19]([CH:18]2[CH2:17][CH2:16][CH2:15][CH:14]([C:26]3[C:31]([CH3:32])=[CH:30][CH:29]=[CH:28][N:27]=3)[N:13]2[CH2:12][C:5]2[CH:6]=[CH:7][C:8]([C:10]#[N:11])=[CH:9][C:4]=2[CH2:3][OH:2])=[N:20][CH:21]=[CH:22][CH:23]=1

Participants

6

Reactant 2

HCID 4148881Lithium borohydrideHCID 674204965-cyano-2-(3,3''-dimethyl-3',4',5',6'-tetrahydro-2'H-[2,2'; 6',2'']terpyridin-1'-ylmethyl)-benzoic acid methyl ester

Product 1

HCID 674215664-(3,3''-dimethyl-3',4',5',6'-tetrahydro-2'H-[2,2'; 6',2'']terpyridin-1'-ylmethyl)-3-hydroxymethyl-benzonitrileYield 87%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolventHCID 14798Sodium HydroxideSolvent

Procedure

Using General Procedure A: A solution of 3,3″-dimethyl-1′,2′,3′,4′,5′,6′-hexahydro-[2,2′;6′,2″]terpyridine (0.260 g, 0.98 mmol), 2-bromomethyl-5-cyano-benzoic acid methyl ester (0.360 g, 1.42 mmol), KI (37 mg, 0.22 mmol), and DIPEA (0.35 mL, 2.01 mmol) in DMF (5 mL) was heated at 60° C. for 17 hours. Purification of the crude material by column chromatography on silica gel (20:1:1 CH2Cl2—CH3OH—NH4OH) provided 415 mg (96%) of 5-cyano-2-(3,3″-dimethyl-3′,4′,5′,6′-tetrahydro-2′H-[2,2′;6′,2″]terpyridin-1′-ylmethyl)-benzoic acid methyl ester as a tan solid. To a cold (0° C.) solution of 5-Cyano-2-(3,3″-dimethyl-3′,4′,5′,6′-tetrahydro-2′H-[2,2′;6′,2″]terpyridin-1′-ylmethyl)-benzoic acid methyl ester (0.409 g, 0.937 mmol) in THF (4.5 mL) and MeOH (9 mL) was added LiBH4 (229 mg, 10.52 mmol) and the mixture was allowed to warm to room temperature overnight. The mixture was diluted with 1.0 N NaOH (10 mL) and extracted with CH2Cl2 (5×25 mL). The combined organic extracts were dried (Na2SO4) and concentrated. Purification of the crude material by column chromatography on silica gel (20:1:1 CH2Cl2—CH3OH—NH4OH) provided 0.332 g (87%) of COMPOUND 56 as a white foam. 1H NMR (CDCl3) δ 1.61-1.77 (m, 3H), 2.05-2.14 (m, 1H), 2.30-2.44 (m, 2H), 2.51 (s, 6H), 3.71 (s, 2H), 4.11 (d, 2H, J=10.8 Hz), 4.46 (s, 2H), 4.94 (br s, 1H), 6.87-6.96 (m, 4H), 7.22-7.27 (m, 3H), 8.21 (d, 2H, J=4.2 Hz). 13C NMR (CDCl3) δ 19.35, 25.70, 28.19, 51.31, 62.24, 67.36, 109.58, 119.48, 122.56, 129.25, 130.02, 132.00, 132.24, 138.53, 139.79, 145.29, 146.76, 159.25; ES-MS m/z 413 (M+H). Anal. Calcd. For C26H28N4O.1.0H2O2: C, 72.53; H, 7.02; N, 13.01. Found: C, 72.46; H, 6.73; N, 12.91.

Workup

  1. extractionextracted with CH2Cl2 (5×25 mL)
  2. dry with materialThe combined organic extracts were dried (Na2SO4)
  3. concentrationconcentrated
  4. customPurification of the crude material by column chromatography on silica gel (20:1:1 CH2Cl2—CH3OH—NH4OH)

Sources & evidence

ORD record
ord-7172d14abd3f4f2d80f3025bec5a3956
Source dataset
uspto-grants-2009_06
Patent number
US07550484B2

Reaction notes

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