1,2-Dichloroethane → HCID 66833037, compound

HRID 1157736Notes

Reaction equation

HRID 1157736 reaction equation
[N:1]1(C(OC(C)(C)C)=O)[CH2:8][CH2:7][CH2:6][C@H:2]1[C:3]([OH:5])=O.O[C:17]1[C:25]2[N:24]=NN[C:21]=2[CH:20]=[CH:19][CH:18]=1.[CH2:26](Cl)[CH2:27]Cl.[CH3:30][CH2:31]N(C(C)C)C(C)C.[C:39]([OH:45])([C:41]([F:44])([F:43])[F:42])=[O:40]>CN(C)C=O.C(Cl)Cl>[F:42][C:41]([F:44])([F:43])[C:39]([OH:45])=[O:40].[C@H:25]1([NH:24][C:3]([C@@H:2]2[CH2:6][CH2:7][CH2:8][NH:1]2)=[O:5])[C:17]2[C:18](=[CH:30][CH:31]=[CH:26][CH:27]=2)[CH2:19][CH2:20][CH2:21]1

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 6422Trifluoroacetic acidHCID 81531DiisopropylethylamineHCID 850831,2-Pyrrolidinedicarboxylic acid, 1-(1,1-dimethylethyl) ester, (2S)-HCID 178418300HCID 178418300, compound

Product 1

HCID 66833037HCID 66833037, compoundYield 95%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

Boc-L-Pro-OH (41.7 g, 0.17 mol), R-tetrahydronapthylamine (31.8 g, 0.22 mol), and hydroxybenzotriazole (28.4 g, 0.18 mol) was dissolved in dimethylformamide (300 mL) and cooled to 0° C. To this cooled reaction mixture was added EDC (41.7 g, 0.22 mol) followed by DiPEA (30.1 mL, 0.17 mol). Reaction was allowed to slowly warm to room temperature and was stirred overnight. Reaction mixture was then partitioned between ethyl acetate and water. The aqueous layer was discarded and the organic layer was washed sequentially with sat. NaHCO3, 0.5 N HCl, and brine. Dried over Na2SO4. Reaction was clean by TLC (50% ethyl acetate/hexanes). Took crude on to next step. Dissolved crude in CH2Cl2 (200 mL) and TFA (200 mL). Within 15 minutes, reaction was baseline by TLC (50% ethyl acetate/hexanes). Removed most of solvent via rotary evaporation. Upon addition of diethyl ether, a white solid crashes out. Filtered solid and washed with diethyl ether. Dried solid under vacuum. Obtained 63 g of desired compound (95% yield over 2 steps). 1H NMR (CD3OH): consistent with proposed structure.

Workup

  1. customTo this cooled reaction mixture
  2. customReaction
  3. temperatureto slowly warm to room temperature
  4. customReaction mixture
  5. customwas then partitioned between ethyl acetate and water
  6. washthe organic layer was washed sequentially with sat. NaHCO3, 0.5 N HCl, and brine
  7. dry with materialDried over Na2SO4
  8. customReaction
  9. waitWithin 15 minutes
  10. customreaction
  11. customRemoved most of solvent via rotary evaporation
  12. additionUpon addition of diethyl ether
  13. filtrationFiltered solid
  14. washwashed with diethyl ether
  15. customDried solid under vacuum

Sources & evidence

ORD record
ord-fba1bac23d1d45fbbb156b3dacaa8978
Source dataset
uspto-grants-2010_10
Patent number
US07807699B2

Reaction notes

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