Hydrochloric Acid → HCID 86618211, compound

HRID 1669520Notes

Reaction equation

HRID 1669520 reaction equation
[C:1]([O:5][C:6](=[O:26])[NH:7][C@H:8]([CH:24]=O)[CH2:9][C:10]1[CH:15]=[CH:14][C:13]([O:16][C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=2)=[CH:12][CH:11]=1)([CH3:4])([CH3:3])[CH3:2].Cl.[NH2:28][OH:29].C(N(CC)CC)C.C([BH3-])#N.[Na+].Cl>C1COCC1.CO.O1CCOCC1>[C:1]([O:5][C:6](=[O:26])[NH:7][C@H:8]([CH2:24][NH:28][OH:29])[CH2:9][C:10]1[CH:15]=[CH:14][C:13]([O:16][C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=2)=[CH:12][CH:11]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 443297Hydroxyamine hydrochlorideHCID 5003444Sodium cyanoborohydrideHCID 86618210HCID 86618210, compound

Product 1

HCID 86618211HCID 86618211, compoundYield 107.5%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution of {(S)-2-[4-(4-chloro-phenoxy)-phenyl]-1-formyl-ethyl}-carbamic acid tert-butyl ester (68 mg, 0.18 mmol, 1 eq.) in THF (0.5 ml) and methanol (4 ml) was added hydroxylamine HCl salt (75 mg, 1 mmol, 5.6 eq.) followed by triethylamine (0.2 ml, 1.5 mmol, 8.3 eq.). The mixture was shaken in a shaker at room temperature overnight. Sodium cyanoborohydride (10 mg, 0.29 mmol, 1.6 eq.) was added in one portion. Then 4 N HCl in dioxane was added dropwise until the reaction mixture was acidic. The mixture was stirred at room temperature for 2 hr. Then the reaction mixture was concentrated to dryness. The residue was partitioned between water and ethyl acetate. NaOH aq. was added to bring pH of the mixture to 10. After excess NH4Cl aq. was added, the mixture was extracted with ethyl acetate. After dried over anhydrous MgSO4, the volatile material was removed under reduced pressure and the residue was purified by chromatography on silica gel using DCM/MeOH (100:1 to 25:1) as eluent to give the desired product (76 mg, 100% yield) as white solid, which was re-purified by chromatography on silica gel using EA/hexane (1:2 to 2:1) followed by EA as eluent to give the desired product (52 mg, 73% yield).

Workup

  1. stirringThe mixture was stirred at room temperature for 2 hr
  2. concentrationThen the reaction mixture was concentrated to dryness
  3. customThe residue was partitioned between water and ethyl acetate
  4. additionNaOH aq. was added
  5. additionAfter excess NH4Cl aq. was added
  6. extractionthe mixture was extracted with ethyl acetate
  7. dry with materialAfter dried over anhydrous MgSO4
  8. customthe volatile material was removed under reduced pressure
  9. customthe residue was purified by chromatography on silica gel

Sources & evidence

ORD record
ord-ab8acdb0fd2f43b59ea083a32c6f2b24
Source dataset
uspto-grants-2011_08
Patent number
US07989480B2

Reaction notes

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