1,2-Dichloroethane → HCID 58920323, compound

HRID 1365498Notes

Reaction equation

HRID 1365498 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C@@:8]([NH:27][C:28](=[O:39])OC2C=CC([N+]([O-])=O)=CC=2)([C:16]2[CH:21]=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:19]=[C:18]([F:26])[CH:17]=2)[CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[N:6][CH:7]=1.ClCCCl.Br.[F:45][C:46]1([F:51])[CH2:50][CH2:49][NH:48][CH2:47]1>>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C@@:8]([NH:27][C:28]([N:48]2[CH2:49][CH2:50][C:46]([F:51])([F:45])[CH2:47]2)=[O:39])([C:16]2[CH:21]=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:19]=[C:18]([F:26])[CH:17]=2)[CH2:9][C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=2)=[N:6][CH:7]=1

Participants

4

Reactant 3

HCID 111,2-DichloroethaneHCID 66934308HCID 66934308, compoundHCID 66934388HCID 66934388, compound

Product 1

HCID 58920323HCID 58920323, compoundYield 17%

Procedure

To a crude solution of (S)-4-nitrophenyl 1-(5-chloropyridin-2-yl)-1-(3-fluoro-5-(trifluoromethyl)phenyl)-2-phenylethylcarbamate in DCE (1 mL) (67 mg, 0.13 mmol) was added 3,3-difluoropyrrolidine hydrobromide (24 mg, 0. 12 mmol). The reaction mixture was stirred at room temperature for 2 h and the solution turned yellow. The solution was concentrated, dissolved in MeOH (1.5 mL), filtered and purified by reverse phase prep. HPLC YMC ODSA 30×100 mm, 20-100% MeOH/H2O (0.1% TFA) gradient over 10 mins at 20 mL/min flow rate. (S)-N-(1-(5-chloropyridin-2-yl)-1-(3-fluoro-5-(trifluoromethyl)phenyl)-2-phenylethyl)-3,3-difluoropyrrolidine-1-carboxamide (0.011 g, 17% yield) eluted at a retention time of 11.2 mins and was isolated as colorless oil. LCMS: 2.15 min [M+1] 528.2 (2 min gradient, MeOH/H2O 0.1% TFA) 1H NMR (CDCl3, 400 MHz): 8.20 (d, J=2.0 Hz, 1H), 7.60 (dd, J=2 Hz, J=8 Hz, 1H), 7.46 (s, 1H), 7.30 (d, J=8 Hz, 1H), 7.15 (m, 2H), 7.05 (m, 1H), 7.03 (m, 3H), 6.44, (d, J=8 Hz, 1H), 4.37, (d, J=12 Hz, 1H), 3.74, (q, J=12 Hz, 1H), 3.54, (m, 1H), 3.44, (m, 2H), 3.32, (q, J=8 Hz, 1H), 2.32, (m, 2H).

Workup

  1. concentrationThe solution was concentrated
  2. dissolutiondissolved in MeOH (1.5 mL)
  3. filtrationfiltered
  4. custompurified by reverse phase prep
  5. waitHPLC YMC ODSA 30×100 mm, 20-100% MeOH/H2O (0.1% TFA) gradient over 10 mins at 20 mL/min flow rate

Sources & evidence

ORD record
ord-9527dbdc5c1c43ce8bba31b2f6a7c1e4
Source dataset
uspto-grants-2011_02
Patent number
US07888376B2

Reaction notes

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