Dimethylformamide → 4-[(R)-3-(2,3-Dihydro-benzo[1,4]dioxin-6-yl)-2-oxo-oxazolidin-5-ylmethyl]-piperazine-1-carboxylic acid tert-butyl ester

HRID 1511796Notes

Reaction equation

HRID 1511796 reaction equation
[CH2:1]([O:8][C:9](=[O:21])[NH:10][C:11]1[CH:20]=[CH:19][C:14]2[O:15][CH2:16][CH2:17][O:18][C:13]=2[CH:12]=1)[C:2]1C=CC=CC=1.[O:22]([C:24]([CH3:27])([CH3:26])[CH3:25])[Li].[CH3:28][N:29]([CH:31]=[O:32])[CH3:30]>>[C:24]([O:22][C:31]([N:29]1[CH2:30][CH2:30][N:29]([CH2:31][C@H:1]2[O:8][C:9](=[O:21])[N:10]([C:11]3[CH:20]=[CH:19][C:14]4[O:15][CH2:16][CH2:17][O:18][C:13]=4[CH:12]=3)[CH2:2]2)[CH2:28][CH2:28]1)=[O:32])([CH3:27])([CH3:26])[CH3:25]

Participants

4

Reactant 3

HCID 6228DimethylformamideHCID 66736198(2,3-Dihydro-benzo[1,4]dioxin-6-yl)-carbamic acid benzyl esterHCID 178506942HCID 178506942, compound

Product 1

HCID 669545294-[(R)-3-(2,3-Dihydro-benzo[1,4]dioxin-6-yl)-2-oxo-oxazolidin-5-ylmethyl]-piperazine-1-carboxylic acid tert-butyl esterYield 36%

Conditions

Temperature
50 °C

Procedure

A solution of piperazine-1-carboxylic acid tert-butyl ester (commercial; 1.40 g, 7.6 mmol) in dry MeOH (25 mL) was treated with MgSO4 (1.9 g). (R)-Epichlorohydrin (1.47 mL, 18.9 mmol) was added dropwise and the mixture was heated at 35° C. for 2 h and was then stirred at rt overnight. The mixture was filtered over Celite and concentrated under reduced pressure. The residue was taken up in DCM and washed with water. The org. phase was dried over MgSO4 and concentrated under reduced pressure to afford the crude 4-((R)-3-chloro-2-hydroxy-propyl)-piperazine-1-carboxylic acid tert-butyl ester. To a solution of the above intermediate chlorohydrin (2.10 g, 7.53 mmol) and (2,3-dihydro-benzo[1,4]dioxin-6-yl)-carbamic acid benzyl ester (2.15 g, 1 eq, prepared according to WO2007107965) in DMF (30 mL) was added LiOtBu (10.3 mL, 2.2M in THF) at rt. The mixture was stirred at rt over night and subsequently at 50° C. for 5 h. The mixture was partitioned between EA and 0.5M HCl. The aq. phase was basified (NH4OH) and extracted with EA. The org. layer was dried over MgSO4 and concentrated under reduced pressure to afford the title compound as a colorless solid (1.15 g, 36%).

Workup

  1. customThe mixture was partitioned between EA and 0.5M HCl
  2. extractionextracted with EA
  3. dry with materiallayer was dried over MgSO4
  4. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-cdf45ef8a68c449ab6b0f3231a1f9696
Source dataset
uspto-grants-2012_07
Patent number
US08217029B2

Reaction notes

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