Trifluoroacetic acid → HCID 23648596, compound

HRID 2096923Notes

Reaction equation

HRID 2096923 reaction equation
[F:1][CH:2]([F:25])[O:3][CH2:4][C@@H:5]([NH:17][C:18](=O)[O:19]C(C)(C)C)[C:6]([NH:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([F:16])=[CH:12][CH:11]=1)=[O:7].F[C:27](F)(F)C(O)=O>ClCCl>[C:18]([NH:17][C@H:5]([CH2:4][O:3][CH:2]([F:25])[F:1])[C:6]([NH:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([F:16])=[CH:12][CH:11]=1)=[O:7])(=[O:19])[CH3:27]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 57539233HCID 57539233, compound

Product 1

HCID 23648596HCID 23648596, compoundYield 65.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Tert-Butyl {(1R)-1-[(difluoromethoxy)methyl]-2-[(4-fluorobenzyl)amino]-2-oxoethyl}carbamate (400 mg, 1.1 mmol) was stirred with trifluoroacetic acid (1.5 mL) and dichloromethane (2.5 mL) in an ice bath for an hour. The reaction mixture was concentrated, mixed with acetic anhydride-pyridine (1:1, 6 mL) at room temperature for 30 minutes and then diluted with ethyl acetate, washed with saturated sodium bicarbonate, brine, 0.5N HCl and brine again. The organic layer was dried, concentrated, and triturated with diethyl ether to give (2R)-2-(acetylamino)-3-(difluoromethoxy)-N-(4-fluorobenzyl)propanamide (220 mg, 65.7%) as a white solid. Mp: 162.7° C. 1H NMR (300 MHz, CDCl3): (ppm) 7.24 (dd, 2H), 7.03 (t, 2H), 6.78 (w, 1H), 6.35 (d, 1H), 6.24 (wt, 1H), 4.71 (m, 1H), 4.44 (d, 2H), 4.24 (dd, 1H), 4.01 (dd, 1H) and 2.05 (s, 3H).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. additionmixed with acetic anhydride-pyridine (1:1, 6 mL) at room temperature for 30 minutes
  3. additiondiluted with ethyl acetate
  4. washwashed with saturated sodium bicarbonate, brine, 0.5N HCl and brine again
  5. customThe organic layer was dried
  6. concentrationconcentrated
  7. customtriturated with diethyl ether

Sources & evidence

ORD record
ord-c8d71c5205b742ff9ce851d4de9c08f4
Source dataset
uspto-grants-2013_05
Patent number
US08450336B2

Reaction notes

Loading…