Triethylamine → (1R,2R)-N-(2,4,6-trimethylphenylsulfonyl)-1,2-diphenylethane-1,2-diamine

HRID 660018Notes

Reaction equation

HRID 660018 reaction equation
[CH3:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[C:4]([CH3:9])[C:3]=1[S:10](Cl)(=[O:12])=[O:11].[C:14]1([C@@H:20]([NH2:29])[C@@H:21]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[NH2:22])[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.C(N(CC)CC)C.C(=O)([O-])[O-].[K+].[K+]>O1CCCC1.CN(C)C=O.ClCCl>[NH2:22][C@H:21]([C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[C@H:20]([NH:29][S:10]([C:3]1[C:2]([CH3:1])=[CH:7][C:6]([CH3:8])=[CH:5][C:4]=1[CH3:9])(=[O:12])=[O:11])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 130462-Mesitylenesulfonyl chlorideHCID 2724998(1R,2R)-(+)-1,2-Diphenylethylenediamine

Product 1

HCID 12165385(1R,2R)-N-(2,4,6-trimethylphenylsulfonyl)-1,2-diphenylethane-1,2-diamineYield 68.2%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of 2,4,6-trimethylbenzene-1-sulfonyl chloride 31 (1.54 g, 7.06 mmol, 0.99 eq) in tetrahydrofuran (75 mL) was added drop-wise at 0° C. over 70 minutes (min) to a suspension of (1R,2R)-1,2-diphenylethane-1,2-diamine 30 (1.5 g, 7.08 mmol, 1.0 eq), triethylamine (2.04 g, 2.8 mL, 2.02 mmol, 0.28 eq) and powdered potassium carbonate (1.60 g, 11.59 mmol, 1.64 eq) in a mixture of tetrahydrofuran (60 mL) and N,N-dimethylformamide (15 mL). When addition was complete the suspension was stirred at 0° C. for 3 hours (h). The reaction mixture was concentrated under reduced pressure to remove most of the tetrahydrofuran. The residual oily solid was partitioned between water (100 mL) and 3:1 ethyl acetate/heptanes. The organic phase was diluted with heptanes (50 mL) and the solution washed with water (3×100 mL) followed by brine (100 mL). The organic solution was dried over sodium sulfate, filtered and the filtrate concentrated under reduced pressure to give a pale yellow oil. The crude product was dissolved in a minimum volume of dichloromethane, adsorbed onto silica gel and dry-loaded on a column of silica gel (50 g) packed in 75% ethyl acetate/heptanes. The column was eluted with 75% ethyl acetate/heptanes (300 mL) and ethyl acetate (300 mL). Product-containing fractions were concentrated under reduced pressure to give a slightly gummy solid that was triturated with hexanes containing a small amount of methyl t-butyl ether, filtered, washed with hexanes and dried to give 1.90 g of 32 as a white solid.

Workup

  1. additionWhen addition
  2. concentrationThe reaction mixture was concentrated under reduced pressure
  3. customto remove most of the tetrahydrofuran
  4. customThe residual oily solid was partitioned between water (100 mL) and 3:1 ethyl acetate/heptanes
  5. additionThe organic phase was diluted with heptanes (50 mL)
  6. washthe solution washed with water (3×100 mL)
  7. dry with materialThe organic solution was dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationthe filtrate concentrated under reduced pressure
  10. customto give a pale yellow oil
  11. washThe column was eluted with 75% ethyl acetate/heptanes (300 mL) and ethyl acetate (300 mL)
  12. concentrationProduct-containing fractions were concentrated under reduced pressure
  13. customto give a slightly gummy solid
  14. customthat was triturated with hexanes containing a small amount of methyl t-butyl ether
  15. filtrationfiltered
  16. washwashed with hexanes
  17. customdried

Sources & evidence

ORD record
ord-cc463ff9a59241deba50baed75037768
Source dataset
uspto-grants-2011_12
Patent number
US08084464B2

Reaction notes

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