Sodium borohydride → HCID 9801831, compound

HRID 430140Notes

Reaction equation

HRID 430140 reaction equation
C([O:3][C:4](=O)[CH2:5][C:6]1[N:7]=[C:8]([NH:11][C:12](=[O:28])[CH:13]([C:20]2[CH:25]=[CH:24][C:23]([Cl:26])=[C:22]([Cl:27])[CH:21]=2)[CH2:14][CH:15]2[CH2:19][CH2:18][CH2:17][CH2:16]2)[S:9][CH:10]=1)C.[BH4-].[Na+]>O1CCCC1>[CH:15]1([CH2:14][CH:13]([C:20]2[CH:25]=[CH:24][C:23]([Cl:26])=[C:22]([Cl:27])[CH:21]=2)[C:12]([NH:11][C:8]2[S:9][CH:10]=[C:6]([CH2:5][CH2:4][OH:3])[N:7]=2)=[O:28])[CH2:19][CH2:18][CH2:17][CH2:16]1

Participants

4

Reactant 2

HCID 4311764Sodium borohydride2×HCID 46221804HCID 46221804, compound

Product 1

HCID 9801831HCID 9801831, compoundYield 58.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
25 °C

Procedure

A solution of {2-[3-cyclopentyl-2-(3,4-dichlorophenyl)-propionylamino]-thiazol-4-yl}-acetic acid ethyl ester (prepared in Example 1 (B)(c), 129 mg, 0.28 mmol) in tetrahydrofuran (1.4 mL) at 25° C. was slowly treated with sodium borohydride (22.5 mg, 0.59 mmol). The resulting reaction mixture was stirred at 25° C. for 10 h. After 10 h at 25° C., a substantial amount of starting material still remained. An additional amount of sodium borohydride powder (21.4 mg, 0.57 mmol) was added to the reaction mixture, and the reaction mixture was heated under reflux for 14 h. The reaction mixture was allowed to cool to 25° C., and then slowly quenched by the dropwise addition of water. The resulting reaction mixture was concentrated in vacuo to remove tetrahydrofuran. The resulting residue was diluted with ethyl acetate (100 mL) and washed with a saturated aqueous sodium chloride solution (1×50 mL). The organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 3/1 then 1/1 hexanes/ethyl acetate) afforded 3-cyclopentyl-2-(3,4-dichlorophenyl)-N-[4-(2-hydroxyethyl)-thiazol-2-yl]-propionamide (68.1 mg, 58%) as a white foam: mp 85-86° C.; FAB-HRMS m/e calcd for C19H22Cl2N2O2S (M+H)+ 413.0858, found 413.0838.

Workup

  1. customThe resulting reaction mixture
  2. waitAfter 10 h at 25° C.
  3. temperaturethe reaction mixture was heated
  4. temperatureunder reflux for 14 h
  5. temperatureto cool to 25° C.
  6. customslowly quenched by the dropwise addition of water
  7. customThe resulting reaction mixture
  8. concentrationwas concentrated in vacuo
  9. customto remove tetrahydrofuran
  10. additionThe resulting residue was diluted with ethyl acetate (100 mL)
  11. washwashed with a saturated aqueous sodium chloride solution (1×50 mL)
  12. dry with materialThe organic layer was dried over sodium sulfate
  13. filtrationfiltered
  14. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-a88e0bc3c1f7417c85596ff6a8eb7b1e
Source dataset
uspto-grants-2001_11
Patent number
US06320050B1

Reaction notes

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