Ammonium Chloride → HCID 57941419, compound

HRID 1438016Notes

Reaction equation

HRID 1438016 reaction equation
C[O:2][C:3](=O)[C:4]1[CH:9]=[CH:8][C:7]([CH2:10][N:11]2[C:19]3[C@:18]4([CH3:23])[C:20]([CH3:22])([CH3:21])[C@@H:15]([CH2:16][CH2:17]4)[C:14]=3[C:13](=[O:24])[N:12]2[C:25]2[CH:30]=[CH:29][C:28]([F:31])=[CH:27][C:26]=2[F:32])=[CH:6][CH:5]=1.[BH4-].[Na+].[Cl-].[NH4+].O.[Cl-].[Na+].O>O1CCCC1.ClCCl.CO>[F:32][C:26]1[CH:27]=[C:28]([F:31])[CH:29]=[CH:30][C:25]=1[N:12]1[C:13](=[O:24])[C:14]2[C@H:15]3[C:20]([CH3:22])([CH3:21])[C@:18]([CH3:23])([CH2:17][CH2:16]3)[C:19]=2[N:11]1[CH2:10][C:7]1[CH:6]=[CH:5][C:4]([CH2:3][OH:2])=[CH:9][CH:8]=1

Participants

8

Reactant 4

HCID 25517Ammonium ChlorideHCID 4311764Sodium borohydride3×HCID 23713072Sodium chloride dihydrateHCID 57941317HCID 57941317, compound

Product 1

HCID 57941419HCID 57941419, compoundYield 43%

Reagents, catalysts & solvents 3

HCID 887MethanolSolvent2×HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
65 °C

Procedure

A mixture of 4-[(4R,7S)-2-(2,4-difluoro-phenyl)-7,8,8-trimethyl-3-oxo-2,3,4,5,6,7-hexahydro-4,7-methano-indazol-1-ylmethyl]-benzoic acid methyl ester (Example 104; 189 mg, 0.42 mmol) and pulverized sodium borohydride (102 mg, 2.7 mmol) in tetrahydrofuran (2 mL) was heated at 65° C. for 15 min. Methanol (2 mL) was added dropwise over a period of 2 min and gas evolution was noted. The mixture was heated at 65° C. for 1 h, and then an additional portion of methanol (1 mL) was added. The mixture was heated at 65° C. for 1 h, and then an additional portion of sodium borohydride (ca. 50 mg) was added. The mixture was heated at 65° C. for 1 h, and then an additional portion of sodium borohydride (ca. 50 mg) was added. The mixture was heated at 65° C. for 1 h, and then it was cooled to room temperature. Saturated aqueous ammonium chloride (6 mL) and dichloromethane (30 mL) were added. The mixture was stirred at room temperature for 10 min. 1:1 Water/brine (20 mL) was added and the mixture was extracted with dichloromethane (3×30 mL). The combined organic extracts were dried (magnesium sulfate), filtered, and evaporated. The residue was purified using an ISCO 12 g column, eluting with 75-100% ethyl acetate/hexanes. Fractions containing the product were concentrated, co-evaporated with ether and petroleum ether, and then dried under high vacuum at 50° C. overnight give (4R,7S)-2-(2,4-difluoro-phenyl)-1-(4-hydroxymethyl-benzyl)-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (76 mg, 43%) as a white solid. ES(+)-MS (M+H) 425.

Workup

  1. temperatureThe mixture was heated at 65° C. for 1 h
  2. temperatureThe mixture was heated at 65° C. for 1 h
  3. temperatureThe mixture was heated at 65° C. for 1 h
  4. temperatureThe mixture was heated at 65° C. for 1 h
  5. temperatureit was cooled to room temperature
  6. extractionthe mixture was extracted with dichloromethane (3×30 mL)
  7. dry with materialThe combined organic extracts were dried (magnesium sulfate)
  8. filtrationfiltered
  9. customevaporated
  10. customThe residue was purified
  11. washeluting with 75-100% ethyl acetate/hexanes
  12. additionFractions containing the product
  13. concentrationwere concentrated, co-evaporated with ether and petroleum ether
  14. customdried under high vacuum at 50° C. overnight

Sources & evidence

ORD record
ord-2e37093398a34dacb4fb967595868f70
Source dataset
uspto-grants-2009_11
Patent number
US07622492B2

Reaction notes

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