Methanol → HCID 21689652, compound

HRID 359394Notes

Reaction equation

HRID 359394 reaction equation
[CH2:1]([CH:3]1[O:5][CH2:4]1)[Cl:2].C([O-])(O)=O.[Na+].[F:11][C:12]1[CH:17]=[CH:16][C:15]([CH:18]([N:26]2[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]2)[C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=2)=[CH:14][CH:13]=1.CO>C(O)C.C(Cl)Cl>[OH2:5].[Cl:2][CH2:1][CH:3]([OH:5])[CH2:4][N:29]1[CH2:28][CH2:27][N:26]([CH:18]([C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=2)[C:15]2[CH:14]=[CH:13][C:12]([F:11])=[CH:17][CH:16]=2)[CH2:31][CH2:30]1

Participants

7

Reactant 4

HCID 887MethanolHCID 7835EpichlorohydrinHCID 1529321-(Bis(4-fluorophenyl)methyl)piperazineHCID 516892Sodium Bicarbonate

Product 1

HCID 21689652HCID 21689652, compoundYield 100.8%

Reagents, catalysts & solvents 2

HCID 702EthanolSolvent2×HCID 6344DichloromethaneSolvent

Procedure

To a mixture of epichlorohydrin (3.5 mL, 0.05 mol) in ethanol (12 mL) at 0° C. (ice bath) and anhydrous NaHCO3 (4.2 g, 0.05 mol), [bis(4-fluorophenyl)methyl]piperazine (14.4 g, 0.05 mol) in ethanol (200 mL) was added dropwise over 45 min under N2. The ice bath was removed and the mixture was allowed to come to room temperature. After 18 h the NaHCO3 was removed by filtration via a sintered glass funnel and the ethanol in the filtrate was removed in vacuo to give the crude product (21.3 g). Silica gel flash chromatography using 2.0% MeOH:CH2Cl2 gave pure product (10.05 g, 52.9%) as an amber oil. DCI/MS (M+1) 381. 400 MHz 1H NMR (CDCl3) δ: 7.3 (m, 4H), 6.95 (m, 4H), 4.2 (s, 1H), 3.95 (m, 1H), 3.55 (m, 2H), 2.7 (m, 2H), 2.5 (m, 4H), 2.4 (m, 4H).

Workup

  1. additionwas added dropwise over 45 min under N2
  2. customThe ice bath was removed
  3. customto come to room temperature
  4. customAfter 18 h the NaHCO3 was removed by filtration via a sintered glass funnel
  5. customthe ethanol in the filtrate was removed in vacuo
  6. customto give the crude product (21.3 g)

Sources & evidence

ORD record
ord-7b43a4571b224a8da6f6c64d25c0fbf5
Source dataset
uspto-grants-1991_03
Patent number
US05001127

Reaction notes

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