Triethylamine → HCID 86759087, compound

HRID 1359036Notes

Reaction equation

HRID 1359036 reaction equation
[CH3:1][O:2][C:3]([C@@H:5]1[CH2:10][CH2:9][N:8]([S:11]([CH2:14][CH2:15][CH2:16][O:17][C:18]2[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=2)(=[O:13])=[O:12])[C@@H:7]([C:25]([OH:27])=O)[CH2:6]1)=[O:4].C(N(CC)CC)C.Cl.[CH2:36]([O:43][NH2:44])[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>C(Cl)Cl.Cl.C(OCC)(=O)C>[CH3:1][O:2][C:3]([C@@H:5]1[CH2:10][CH2:9][N:8]([S:11]([CH2:14][CH2:15][CH2:16][O:17][C:18]2[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=2)(=[O:13])=[O:12])[C@@H:7]([C:25](=[O:27])[NH:44][O:43][CH2:36][C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[CH2:6]1)=[O:4]

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 102312Benzyloxyamine hydrochlorideHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 70024845HCID 70024845, compound

Product 1

HCID 86759087HCID 86759087, compoundYield 66.4%

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of (2R,4R)-1-[3-(4-fluorophenoxy)-propane-1-sulfonyl]-piperidine-2,4-dicarboxylic acid 4-methyl ester (970 mg, 2.4 mmol) in 5 mL of methylene chloride was added triethylamine (1.0 mL, 7.2 mmol) and O-benzylhydroxylamine hydrochloride (410 mg, 2.64 mmol) at ambient temperature (22° C.) To the resulting solution was added benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate (1.17 g, 2.64 mmol) and the mixture was stirred for 16 hours under a nitrogen atmosphere. The mixture was diluted with 25 mL of 1 N hydrochloric acid and 25 mL of ethyl acetate. The organic layer was removed and the aqueous layer was extracted with ethyl acetate (2×). The combined organic layers were washed with saturated aqueous sodium carbonate (1×) and brine (1×). The organic layer was dried (sodium sulfate), filtered, and the filtrate was concentrated in vacuo. Purification of the viscous yellow residue by flash chromatography (eluting with 1:1 ethyl acetate/hexanes) gave 810 mg of (2R,4R)-2-benzyloxycarbamoyl-1-[3-(4-fluorophenoxy)-propane-1-sulfonyl]-piperidine-4-carboxylic acid methyl ester as a clear oil.

Workup

  1. customThe organic layer was removed
  2. extractionthe aqueous layer was extracted with ethyl acetate (2×)
  3. washThe combined organic layers were washed with saturated aqueous sodium carbonate (1×) and brine (1×)
  4. dry with materialThe organic layer was dried (sodium sulfate)
  5. filtrationfiltered
  6. concentrationthe filtrate was concentrated in vacuo
  7. customPurification of the viscous yellow residue
  8. washby flash chromatography (eluting with 1:1 ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-417c2a4739864c26a1c8adafe5a13e31
Source dataset
uspto-grants-2003_07
Patent number
US06599890B1

Reaction notes

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