Methanol → HCID 19785542, compound

HRID 256775Notes

Reaction equation

HRID 256775 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([CH:8]([CH3:16])[C:9](=O)[CH2:10][CH2:11][C:12]([OH:14])=[O:13])[CH:5]=[CH:4][C:3]=1[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.BrBr.[CH3:25][NH:26][C:27]([NH2:29])=[S:28].CO.[CH2:32](OCC)[CH3:33]>>[F:1][C:2]1[CH:7]=[C:6]([CH:8]([C:9]2[N:29]=[C:27]([NH:26][CH3:25])[S:28][C:10]=2[CH2:11][C:12]([O:14][CH2:32][CH3:33])=[O:13])[CH3:16])[CH:5]=[CH:4][C:3]=1[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1

Participants

6

Reactant 5

HCID 887MethanolHCID 3283Diethyl EtherHCID 24408BromineHCID 2723704MethylthioureaHCID 19785566HCID 19785566, compound

Product 1

HCID 19785542HCID 19785542, compoundYield 35%

Procedure

To an ice-cooled solution of 5-(2-fluoro-4-biphenylyl)-4-oxohexanoic acid (500 mg, 1.52 mmoles) in diethyl ether (10 ml) was added dropwise bromine (243 mg, 1.52 mmoles) and the resulting mixture was stirred at room temperature for 3.5 hours. The reaction mixture was concentrated under reduced pressure. A mixture of the afforded residue, N-methylthiourea (164 mg, 1.82 mmoles) and methanol was stirred at 50° C. for 2 hours and concentrated under reduced pressure. The residue was partitioned between ethyl acetate and aqueous sodium bicarbonate. The organic layer was washed with water, dried over sodium sulfate and concentrated under reduce pressure. Purification of the residue by medium pressure silica gel column chromatography gave the desired ethyl 2-(4-(1-(2-fluoro-4-biphenylyl)ethyl)-2-methylamino-5-thiazolyl)acetate (209 mg, 0.524 mmole, yield 35%) as a yellow oil.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. stirringwas stirred at 50° C. for 2 hours
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was partitioned between ethyl acetate and aqueous sodium bicarbonate
  5. washThe organic layer was washed with water
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated
  8. customPurification of the residue by medium pressure silica gel column chromatography

Sources & evidence

ORD record
ord-4d4587232178424baa5731f6b33f3622
Source dataset
uspto-grants-1993_11
Patent number
US05258396

Reaction notes

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