Triethylamine → Methyl 2-[(4-fluorophenyl)carbonylamino]-3-hydroxypropanoate

HRID 1795021Notes

Reaction equation

HRID 1795021 reaction equation
[F:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[CH:4][CH:3]=1.Cl.[CH3:12][O:13][C:14](=[O:19])[C@H:15]([CH2:17][OH:18])[NH2:16].O.ON1C2C=CC=CC=2N=N1.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.C(N(CC)CC)C>CN(C1C=CC=CN=1)C.O1CCCC1>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:6]([NH:16][CH:15]([CH2:17][OH:18])[C:14]([O:13][CH3:12])=[O:19])=[O:8])=[CH:9][CH:10]=1

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 99734-Fluorobenzoic AcidHCID 2723730L-Serine, methyl ester, hydrochloride (1:1)HCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 27960291-Hydroxybenzotriazole hydrate

Product 1

HCID 22184746Methyl 2-[(4-fluorophenyl)carbonylamino]-3-hydroxypropanoateYield 95.7%

Reagents, catalysts & solvents 2

HCID 218852-DimethylaminopyridineCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To 50 ml of tetrahydrofuran was added 4-fluorobenzoic acid (3.64 g, 26 mmol), L-serine methyl ester hydrochloride (2 g, 13 mmol), 1-hydroxybenzotriazole hydrate (4 g, 26 mmol), O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium hexafluorophosphate (9.9 g, 26 mmol), triethylamine (3.5 ml, 26 mmol) and dimethylaminopyridine (20 mg, 0.16 mmol). The reaction was stirred for 24 hours at room temperature. Solvent was removed under reduced pressure, and the residue dissolved in 150 ml of ethyl acetate. The organic solution was washed in a separatory funnel in the following manner: 3×100 ml 10% aqueous citric acid, 3×100 ml saturated sodium bicarbonate, 3×100 ml water, 1×75 ml saturate sodium chloride solution. The organic layer was concentrated and purified using a Flash40 column (1:2 EtOAc:Hexane, 20 psi) to yield 3 grams of methyl 2-[(4-fluorophenyl)carbonylamino]-3-hydroxypropanoate.

Workup

  1. customSolvent was removed under reduced pressure
  2. dissolutionthe residue dissolved in 150 ml of ethyl acetate
  3. washThe organic solution was washed in a separatory funnel in the following manner
  4. concentration3×100 ml 10% aqueous citric acid, 3×100 ml saturated sodium bicarbonate, 3×100 ml water, 1×75 ml saturate sodium chloride solution
  5. concentrationThe organic layer was concentrated
  6. custompurified

Sources & evidence

ORD record
ord-19e430926aad4bfaaa1bde40ad332587
Source dataset
uspto-grants-2006_04
Patent number
US07026321B2

Reaction notes

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