Lithium borohydride → HCID 57877635, compound

HRID 2266750Notes

Reaction equation

HRID 2266750 reaction equation
[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([N:10]2[CH:14]=[C:13]([C:15]([N:17]3[CH2:22][CH2:21][N:20](C(OCC4C=CC=CC=4)=O)[CH2:19][C@@H:18]3[CH2:33][OH:34])=[O:16])[N:12]=[C:11]2[C:35]2[CH:40]=[CH:39][C:38]([CH3:41])=[CH:37][CH:36]=2)[CH:7]=[CH:8][CH:9]=1)[CH3:2].[CH2:42]([O:44]C1C=C(N2C=C(C(N3CCN(C(OCC4C=CC=CC=4)=O)C[C@@H]3C(OC)=O)=O)N=C2C2C=CC(C)=CC=2)C=CC=1)[CH3:43].[BH4-].[Li+]>CO>[C:42]([O:34][CH2:33][C@H:18]1[CH2:19][NH:20][CH2:21][CH2:22][N:17]1[C:15]([C:13]1[N:12]=[C:11]([C:35]2[CH:40]=[CH:39][C:38]([CH3:41])=[CH:37][CH:36]=2)[N:10]([C:6]2[CH:7]=[CH:8][CH:9]=[C:4]([O:3][CH2:1][CH3:2])[CH:5]=2)[CH:14]=1)=[O:16])(=[O:44])[CH3:43]

Participants

5

Reactant 3

HCID 4148881Lithium borohydride2×HCID 86761244HCID 86761244, compoundHCID 86761246HCID 86761246, compound

Product 1

HCID 57877635HCID 57877635, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Benzyl (3R)-4-{[1-(3-ethoxyphenyl)-2-(4-methylphenyl)-1H-imidazol-4-yl]carbonyl}-3-(hydroxymethyl)piperazine-1-carboxylate To a solution of 4.10 g (7.04 mmol) of 1-benzyl 3-methyl (3R)-4-{[1-(3-ethoxyphenyl)-2-(4-methylphenyl)-1H-imidazol-4-yl]carbonyl}piperazine-1,3-dicarboxylate from Step A in 75 mL of anhydrous methanol at 0° C. under a nitrogen atmosphere was added 460 mg (21.1 mmol) of lithium borohydride. An additional 460 mg (21.1 mmol) of lithium borohydride was added to the reaction mixture every hour for 3 hours and stirred for one hour after the final addition. The reaction was quenched with a saturated aqueous ammonium chloride solution (50 mL) followed by concentration in vacuo to remove the methanol. The residue was diluted with water (15 mL) and extracted with dichloromethane (2×75 mL). The combined organic layers were washed with brine (50 mL), dried over magnesium sulfate, filtered and concentrated in vacuo. The crude residue was purified on a Biotage® purification apparatus (silica gel, 65% ethyl acetate in hexanes) to yield the title compound as a colorless solid. LC/MS 555.2 (M+1).

Workup

  1. additionaddition
  2. customThe reaction was quenched with a saturated aqueous ammonium chloride solution (50 mL)
  3. concentrationfollowed by concentration in vacuo
  4. customto remove the methanol
  5. additionThe residue was diluted with water (15 mL)
  6. extractionextracted with dichloromethane (2×75 mL)
  7. washThe combined organic layers were washed with brine (50 mL)
  8. dry with materialdried over magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe crude residue was purified on a Biotage® purification apparatus (silica gel, 65% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-4e2ececebe704ffe8d545cd229a07fa3
Source dataset
uspto-grants-2010_12
Patent number
US07858629B2

Reaction notes

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