Methyl fluoroacetate → HCID 178520914, compound

HRID 1909427Notes

Reaction equation

HRID 1909427 reaction equation
[F:1][CH2:2][C:3](OC)=[O:4].O([Si](C)(C)C)[K].Cl.[O:14]1[C:18]2[CH:19]=[CH:20][CH:21]=[C:22]([CH:23]3[CH2:28][CH2:27][N:26]([CH2:29][CH2:30][C@H:31]4[CH2:36][CH2:35][C@H:34]([NH2:37])[CH2:33][CH2:32]4)[CH2:25][CH2:24]3)[C:17]=2[O:16][CH2:15]1.C(N(CC)C(C)C)(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C([O-])(O)=O.[Na+]>O1CCOCC1>[O:14]1[C:18]2[CH:19]=[CH:20][CH:21]=[C:22]([CH:23]3[CH2:28][CH2:27][N:26]([CH2:29][CH2:30][C@H:31]4[CH2:32][CH2:33][C@H:34]([NH:37][C:3](=[O:4])[CH2:2][F:1])[CH2:35][CH2:36]4)[CH2:25][CH2:24]3)[C:17]=2[O:16][CH2:15]1

Participants

8

Reactant 6

HCID 9959Methyl fluoroacetateHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 178479251HCID 178479251, compound2×HCID 178504318HCID 178504318, compound

Product 1

HCID 178520914HCID 178520914, compoundYield 66.7%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A mixture of methyl 2-fluoroacetate (11.3 mg, 123 μmol, Eq: 1.5) and KOSiMe3 (21 mg, 164 μmol, Eq: 2) in Dioxane (1 ml) was stirred at room temperature over night. Trans-4-[2-(4-Benzo[1,3]dioxol-4-yl-piperidin-1-yl)-ethyl]-cyclohexylamine hydrochloride (Intermediate A) (30 mg, 81.8 μmol), N,N-diisopropylethylamine (42.3 mg, 57.0 μl, 327 μmol, Eq: 4) and TBTU (39.4 mg, 123 μmol, Eq: 1.5) were added. Reaction mixture was stirred 4 h at room temperature. The reaction mixture was solved with sat NaHCO3 (1×10 mL) and extracted with dichloromethane (2×20 mL). The organic layers were dried over MgSO4 and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 10 g, 0% to 20% MeOH in dichloromethane) to yield the title compound as an off-white solid (21.3 mg, 66.7%), MS (ISP) m/z=391.2 [(M+H)+].

Workup

  1. customReaction mixture
  2. stirringwas stirred 4 h at room temperature
  3. extractionextracted with dichloromethane (2×20 mL)
  4. dry with materialThe organic layers were dried over MgSO4
  5. concentrationconcentrated in vacuo
  6. customThe crude material was purified by flash chromatography (silica gel, 10 g, 0% to 20% MeOH in dichloromethane)

Sources & evidence

ORD record
ord-0566a8f358414610984b94cc673c4691
Source dataset
uspto-grants-2013_12
Patent number
US08598357B2

Reaction notes

Loading…