Methanol → HCID 21689652, compound

HRID 476620Notes

Reaction equation

HRID 476620 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-9b8e5677af8d434fb2588fb44a3379bd
Source dataset
uspto-grants-1989_12
Patent number
US04885300

Reaction notes

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