Lithium tri-s-butylborohydride → HCID 58573835, compound

HRID 932208Notes

Reaction equation

HRID 932208 reaction equation
CCC(C)[BH-](C(C)CC)C(C)CC.[Li+].[Cl:15][C:16]1[CH:17]=[C:18]([C@@H:22]2[C@@H:27]([C:28]3[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][CH:29]=3)[N:26]([C@@H:35]([CH:39]3[CH2:41][CH2:40]3)[C:36](=[O:38])[CH3:37])[C:25](=[O:42])[C@:24]([CH2:44][C:45]([OH:47])=[O:46])([CH3:43])[CH2:23]2)[CH:19]=[CH:20][CH:21]=1>C1COCC1>[Cl:15][C:16]1[CH:17]=[C:18]([C@@H:22]2[C@@H:27]([C:28]3[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][CH:29]=3)[N:26]([C@@H:35]([CH:39]3[CH2:41][CH2:40]3)[C@@H:36]([OH:38])[CH3:37])[C:25](=[O:42])[C@:24]([CH2:44][C:45]([OH:47])=[O:46])([CH3:43])[CH2:23]2)[CH:19]=[CH:20][CH:21]=1

Participants

4

Reactant 2

HCID 3611392Lithium tri-s-butylborohydrideHCID 58573925HCID 58573925, compound

Product 1

HCID 58573835HCID 58573835, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

L-Selectride® (Aldrich, St. Louis, Mo.), (1M in THF, 5.0 ml, 5.00 mmol) was added dropwise over the course of 5 minutes to a solution of 2-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-cyclopropyl-2-oxopropyl)-3-methyl-2-oxopiperidin-3-yl)acetic acid (Example 257, Step E, 1.035 g, 2.12 mmol) in THF (35 ml) at −78° C. After 90 min, the mixture was allowed to warm to 0° C. and was carefully quenched by the addition of saturated ammonium chloride. The aqueous phase was extracted three times with ethyl acetate. The combined organic layer was washed with 1 M HCl, water, sat. aq. NaCl solution and dried over sodium sulfate. After concentration in vacuo, the residue was purified by silica chromatography eluting with a gradient of isopropanol in hexanes. Fractions containing the major isomer were concentrated and then lyophilized from acetonitrile/water to provide the title compound as a white powder. Stereochemistry assigned by analogy to Example 152.

Workup

  1. customwas carefully quenched by the addition of saturated ammonium chloride
  2. extractionThe aqueous phase was extracted three times with ethyl acetate
  3. washThe combined organic layer was washed with 1 M HCl, water, sat. aq. NaCl solution
  4. dry with materialdried over sodium sulfate
  5. concentrationAfter concentration in vacuo
  6. customthe residue was purified by silica chromatography
  7. washeluting with a gradient of isopropanol in hexanes
  8. additionFractions containing the major isomer
  9. concentrationwere concentrated

Sources & evidence

ORD record
ord-0fa26d43bbe44272851dcf2f814c461c
Source dataset
uspto-grants-2016_03
Patent number
US09296736B2

Reaction notes

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