Lithium Chloride → tert-Butyl (2S,4S)-2-(hydroxymethyl)-4-{[(1-isopropyl-1H-indazol-3-yl)carbonyl]amino}pyrrolidine-1-carboxylate

HRID 602467Notes

Reaction equation

HRID 602467 reaction equation
[CH:1]([N:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6]([C:13]([NH:15][C@@H:16]2[CH2:20][N:19]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[C@H:18]([C:28](OC)=[O:29])[CH2:17]2)=[O:14])=[N:5]1)([CH3:3])[CH3:2].[Cl-].[Li+].[BH4-].[Na+]>O1CCCC1CO>[OH:29][CH2:28][C@@H:18]1[CH2:17][C@H:16]([NH:15][C:13]([C:6]2[C:7]3[C:12](=[CH:11][CH:10]=[CH:9][CH:8]=3)[N:4]([CH:1]([CH3:2])[CH3:3])[N:5]=2)=[O:14])[CH2:20][N:19]1[C:21]([O:23][C:24]([CH3:26])([CH3:25])[CH3:27])=[O:22]

Participants

5

Reactant 3

HCID 433294Lithium Chloride2×HCID 4311764Sodium borohydride2×HCID 866241491-tert-Butyl 2-methyl (2S,4S)-4-{[(1-isopropyl-1H-indazol-3-yl)carbonyl]amino}pyrrolidine-1,2-dicarboxylate

Product 1

HCID 67270520tert-Butyl (2S,4S)-2-(hydroxymethyl)-4-{[(1-isopropyl-1H-indazol-3-yl)carbonyl]amino}pyrrolidine-1-carboxylateYield 93%

Reagents, catalysts & solvents 1

HCID 7360Tetrahydrofurfuryl alcoholSolvent

Procedure

To a stirred solution of 1-tert-butyl 2-methyl (2S,4S)-4-{[(1-isopropyl-1H-indazol-3-yl)carbonyl]amino}pyrrolidine-1,2-dicarboxylate (135 mg, 0.313 mmol, step 1 of Example 7) in tetrahydrofuran-methanol (2 mL-2 mL) were added lithium chloride (81 mg, 1.92 mmol) and sodium borohydride (73 mg, 1.92 mmol) at room temperature. The resulting mixture was stirred at the same temperature for 20 h. Another lithium chloride (81 mg, 1.92 mmol) and sodium borohydride (73 mg, 1.92 mmol) were added to the mixture at room temperature. After stirring for 3 h, the mixture was quenched with water (10 mL), extracted with ethyl acetate (100 mL). The organic layer was washed with brine (10 mL), dried over sodium sulfate, and concentrated under reduced pressure. The resulting residue was chromatographed on a column of silica gel eluting with n-hexane/ethyl acetate (1:1) to give 117 mg (93%) of the title compound as a colorless oil.

Workup

  1. stirringAfter stirring for 3 h
  2. customthe mixture was quenched with water (10 mL)
  3. extractionextracted with ethyl acetate (100 mL)
  4. washThe organic layer was washed with brine (10 mL)
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe resulting residue was chromatographed on a column of silica gel eluting with n-hexane/ethyl acetate (1:1)

Sources & evidence

ORD record
ord-0809d0442057451fab45fc65d8057a0a
Source dataset
uspto-grants-2011_03
Patent number
US07906532B2

Reaction notes

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