1,2-Dichloroethane → HCID 69373014, compound

HRID 1372470Notes

Reaction equation

HRID 1372470 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([C@H:13]([C:17]1[CH:22]=[CH:21][C:20]([C:23]2[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=2)=[CH:19][CH:18]=1)/[CH:14]=[CH:15]/[CH3:16])[C:10]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.Cl.[F:45][C@H:46]1[CH2:50][CH2:49][NH:48][CH2:47]1.CCN(C(C)C)C(C)C>ClCCl>[C:1]([O:5][C:6]([NH:8][C@@H:9]([C@H:13]([C:17]1[CH:18]=[CH:19][C:20]([C:23]2[CH:24]=[CH:25][C:26]([F:29])=[CH:27][CH:28]=2)=[CH:21][CH:22]=1)[CH:14]=[CH:15][CH3:16])[C:10]([N:48]1[CH2:49][CH2:50][C@H:46]([F:45])[CH2:47]1)=[O:12])=[O:7])([CH3:2])([CH3:4])[CH3:3]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 16217739(s)-3-Fluoropyrrolidine hydrochlorideHCID 69371571HCID 69371571, compound

Product 1

HCID 69373014HCID 69373014, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To 2.11 g (5.49 mmol) of the acid from Step F dissolved in anhydrous dichloromethane (100 mL) was added EDC (1.34 g, 7.0 mmol), HOBT (0.95 g, 7.0 mmol), (3S)-3-fluoropyrrolidine hydrochloride (880 mg, 7.0 mmol) and N,N′-diisopropylethylamine (1.1 mL, 7.0 mmol). After stirring for 48 h at room temperature, the reaction mixture was concentrated and diluted with 100 mL of 10% aqueous hydrochloric acid. The resultant mixture was then extracted with three 150-mL portions of ethyl acetate, the organic phases combined and washed sequentially with 5% hydrochloric acid, saturated aqueous sodium bicarbonate solution, and saturated aqueous brine (100 mL each). The organic phase was then dried over magnesium sulfate, filtered, and evaporated in vacuo to yield the crude material as a viscous oil. The crude material was purified by flash chromatography on a Biotage® system (silica gel, 0 to 40% ethyl acetate/hexanes gradient) to give the title compound as a colorless solid. LC/MS 471.3 (M+1).

Workup

  1. concentrationthe reaction mixture was concentrated
  2. additiondiluted with 100 mL of 10% aqueous hydrochloric acid
  3. extractionThe resultant mixture was then extracted with three 150-mL portions of ethyl acetate
  4. washwashed sequentially with 5% hydrochloric acid, saturated aqueous sodium bicarbonate solution, and saturated aqueous brine (100 mL each)
  5. dry with materialThe organic phase was then dried over magnesium sulfate
  6. filtrationfiltered
  7. customevaporated in vacuo
  8. customto yield the crude material as a viscous oil
  9. customThe crude material was purified by flash chromatography on a Biotage® system (silica gel, 0 to 40% ethyl acetate/hexanes gradient)

Sources & evidence

ORD record
ord-d8cee54187ef4266acf85d336c23e168
Source dataset
uspto-grants-2007_01
Patent number
US07157490B2

Reaction notes

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