Lithium borohydride → HCID 57545941, compound

HRID 913923Notes

Reaction equation

HRID 913923 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]([CH:11]([O:16][CH2:17][C:18]2([C:31]3[CH:36]=[CH:35][C:34]([F:37])=[CH:33][CH:32]=3)[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:20][CH2:19]2)[C:12](OC)=[O:13])[C:8]2[C:4](=[CH:5][N:6]([CH2:38][O:39][CH2:40][CH2:41][Si:42]([CH3:45])([CH3:44])[CH3:43])[N:7]=2)[CH:3]=1.[BH4-].[Li+]>O1CCCC1.CO>[Cl:1][C:2]1[CH:10]=[C:9]([CH:11]([O:16][CH2:17][C:18]2([C:31]3[CH:36]=[CH:35][C:34]([F:37])=[CH:33][CH:32]=3)[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:20][CH2:19]2)[CH2:12][OH:13])[C:8]2[C:4](=[CH:5][N:6]([CH2:38][O:39][CH2:40][CH2:41][Si:42]([CH3:45])([CH3:43])[CH3:44])[N:7]=2)[CH:3]=1

Participants

5

Reactant 2

HCID 4148881Lithium borohydrideHCID 57546118HCID 57546118, compound

Product 1

HCID 57545941HCID 57545941, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of tert-butyl 4-((1-(5-chloro-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-7-yl)-2-methoxy-2-oxoethoxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate (850 mg, 1.28 mmol) in tetrahydrofuran (7.4 mL) and methanol (0.37 mL) at 0° C. was added lithium borohydride (55.9 mg, 2.57 mmol). The ice bath was removed and stirring continued for 30 min. The reaction was diluted with diethyl ether and quenched by addition of saturated ammonium chloride. The ethereal was washed with water, then brine, dried over magnesium sulfate, and concentrated. Column chromatography (25%→50% ethyl acetate/n-hexane) gave 794 mg (98%) as a foam solid. 1H-NMR (CDCl3, 500 MHz) δ 8.01 (s, 1H), 7.52 (d, J=1.5 Hz, 1H), 7.33 (dd, J=8.6, 5.2 Hz, 2H), 7.05 (dd, J=8.6, 8.5 Hz, 2H), 6.75 (s, 1H), 5.65 (d, J=10.7 Hz, 1H), 5.62 (d, J=10.7 Hz, 1H), 4.95 (dd, J=7.0, 3.4 Hz, 1H), 3.55-3.85 (m, 6H), 3.52 (d, J=8.9 Hz, 1H), 3.41 (d, J=8.9 Hz, 1H), 3.06 (m, 2H), 2.10-2.35 (m, 3H), 1.88 (m, 2H), 1.43 (s, 9H), 0.90 (t, J=8.2 Hz, 2H), −0.06 (s, 9H); 13C NMR (126 MHz, CDCl3) δ ppm 161.5 (d, J=246 Hz), 155.0, 145.7, 138.6, 130.2, 128.8 (d, J=7.7 Hz), 128.1, 124.2, 122.8, 122.5, 118.5, 115.4 (d, J=21 Hz), 81.9, 79.5, 79.1, 78.6, 67.7, 66.2, 41.5, 40.0, 32.3, 32.2, 28.6, 17.9, −1.4. Mass spec.: 634.38 (MH)+.

Workup

  1. customThe ice bath was removed
  2. additionThe reaction was diluted with diethyl ether
  3. customquenched by addition of saturated ammonium chloride
  4. washThe ethereal was washed with water
  5. dry with materialbrine, dried over magnesium sulfate
  6. concentrationconcentrated
  7. customColumn chromatography (25%→50% ethyl acetate/n-hexane) gave 794 mg (98%) as a foam solid

Sources & evidence

ORD record
ord-715618c7a1eb4d3881b86f8684c465b9
Source dataset
uspto-grants-2011_09
Patent number
US08026257B2

Reaction notes

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