1,2-Dichloroethane → (R)-N-(tert-Butoxycarbonyl)-4-[(1-methyl-2,2,2-trifluoro-ethylcarbamoyl)-methyl]-benzylamine

HRID 1191045Notes

Reaction equation

HRID 1191045 reaction equation
[C:1]([O:5][C:6]([NH:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([CH2:16][C:17]([OH:19])=O)=[CH:12][CH:11]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.Cl.[CH3:42][C@@H:43]([NH2:48])[C:44]([F:47])([F:46])[F:45]>C(Cl)Cl.CN(C1C=CN=CC=1)C>[C:1]([O:5][C:6]([NH:8][CH2:9][C:10]1[CH:11]=[CH:12][C:13]([CH2:16][C:17](=[O:19])[NH:48][C@H:43]([CH3:42])[C:44]([F:47])([F:46])[F:45])=[CH:14][CH:15]=1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 27559832-(4-((((Tert-butoxy)carbonyl)amino)methyl)phenyl)acetic acidHCID 44593757(2R)-1,1,1-Trifluoropropan-2-amine--hydrogen chloride (1/1)

Product 1

HCID 58495584(R)-N-(tert-Butoxycarbonyl)-4-[(1-methyl-2,2,2-trifluoro-ethylcarbamoyl)-methyl]-benzylamineYield 68.3%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

Dissolve [4-(tert-butoxycarbonylamino-methyl)-phenyl]-acetic acid (190 mg, 0.63 mmol) in DCM (12.4 mL) and add triethylamine (354 μL, 2.5 mmol), DMAP (8 mg, 0.063 mmol), EDC (145 mg, 0.756 mmol), HOBt (102 mg, 0.756 mmol) and (R)-1-methyl-2,2,2-trifluoro-ethylamine hydrochloride (71 mg, 0.63 mmol) under nitrogen atmosphere. Stir the reaction overnight at room temperature. Concentrate in vacuo and purify by chromatography on silica gel eluting with hexane/EtOAc (1:1 and 0:1) to obtain the desired intermediate (155 mg, 68%).

Workup

  1. customthe reaction overnight at room temperature
  2. concentrationConcentrate in vacuo
  3. custompurify by chromatography on silica gel eluting with hexane/EtOAc (1:1 and 0:1)

Sources & evidence

ORD record
ord-326b17d185d1400195a1aee386bf9c84
Source dataset
uspto-grants-2014_03
Patent number
US08680091B2

Reaction notes

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