Trifluoroacetic acid → 2,2-dichloro-N-((1R,2S)-3-fluoro-1-hydroxy-1-(4'-(pyrrolidin-2-yl)-[1,1'-biphenyl]-4-yl)propan-2-yl)acetamide

HRID 2283174Notes

Reaction equation

HRID 2283174 reaction equation
[Cl:1][CH:2]([Cl:35])[C:3]([NH:5][C@H:6]([CH2:33][F:34])[C@@H:7]([C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:20]=[CH:19][C:18]([CH:21]3[CH2:25][CH2:24][CH2:23][N:22]3C(OC(C)(C)C)=O)=[CH:17][CH:16]=2)=[CH:11][CH:10]=1)[OH:8])=[O:4].C(O)(C(F)(F)F)=O>C(Cl)Cl>[Cl:35][CH:2]([Cl:1])[C:3]([NH:5][C@H:6]([CH2:33][F:34])[C@H:7]([OH:8])[C:9]1[CH:10]=[CH:11][C:12]([C:15]2[CH:20]=[CH:19][C:18]([CH:21]3[CH2:25][CH2:24][CH2:23][NH:22]3)=[CH:17][CH:16]=2)=[CH:13][CH:14]=1)=[O:4]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 89519230tert-butyl 2-(4'-((1R,2S)-2-(2,2-dichloroacetamido)-3-fluoro-1-hydroxypropyl)-[1,1'-biphenyl]-4-yl)pyrrolidine-1-carboxylate

Product 1

HCID 895151842,2-dichloro-N-((1R,2S)-3-fluoro-1-hydroxy-1-(4'-(pyrrolidin-2-yl)-[1,1'-biphenyl]-4-yl)propan-2-yl)acetamideYield 84.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of the product of step 1 (210 mg, 0.4 mmol) in DCM (3 mL) is added TFA (1 mL). The mixture is stirred for 1 hour. The reaction is then diluted with DCM, washed with sat.NaHCO3 (aq.) and evaporated to give the title compound (144 mg). 1H-NMR (400 MHz, DMSO) δ(ppm) 1.5-1.65 (1H), 1.7-1.9 (2H), 2.1-2.25 (1H), 2.8-3.0 (1H), 3.0-3.2 (1H), 4.05-4.15 (1H), 4.15-4.35 (1.5H), 4.35-4.45 (0.5H), 4.5-4.6 (0.5H), 4.65-4.75 (0.5H), 4.8-4.9 (1H), 5.9-6.0 (1H), 6.5 (1H), 7.4-7.5 (4H), 7.5-7.65 (4H), 8.6 (1H).

Workup

  1. washwashed
  2. customNaHCO3 (aq.) and evaporated

Sources & evidence

ORD record
ord-c6bc5b5d7a784f2c9578c79887d3bbe1
Source dataset
uspto-grants-2015_09
Patent number
US09145355B2

Reaction notes

Loading…