Triethylamine → HCID 57539233, compound

HRID 601972Notes

Reaction equation

HRID 601972 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([CH2:13][O:14][CH:15]([F:17])[F:16])[C:10]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.ClC(OCC(C)C)=O.[F:33][C:34]1[CH:41]=[CH:40][C:37]([CH2:38][NH2:39])=[CH:36][CH:35]=1>C1COCC1.C(OCC)(=O)C>[F:16][CH:15]([F:17])[O:14][CH2:13][C@@H:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:2])([CH3:3])[CH3:4])[C:10]([NH:39][CH2:38][C:37]1[CH:40]=[CH:41][C:34]([F:33])=[CH:35][CH:36]=1)=[O:12]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 62365Isobutyl chloroformateHCID 673264-FluorobenzylamineHCID 57539230HCID 57539230, compound

Product 1

HCID 57539233HCID 57539233, compoundYield 80%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (2R)-2-[(tert-butoxycarbonyl)amino]-3-(difluoromethoxy)propanoic acid (780 mg, 3.05 mmol) and triethylamine (924 mg, 9.15 mmol) in THF (15 mL) at −78° C., isobutyl chloroformate (417.7 mg, 3.05 mmol) was added dropwise. After 30 minutes, (4-fluorobenzyl)amine (458 mg, 3.0 mmol) was added and the reaction mixture allowed to warm up to room temperature. The mixture was then diluted with ethyl acetate and washed with water, 0.5N HCl and Brine. The organic layer was dried over magnesium sulphate, concentrated, and triturated with hexanes (1:3) to give tert-butyl {(1R)-1-[(difluoromethoxy)methyl]-2-[(4-fluorobenzyl)amino]-2-oxoethyl}carbamate (870 mg, 78.7%) as a white solid. 1H NMR (300 MHz, CDCl3): δ(ppm) 7.23 (dd, 2H), 7.03 (t, 2H), 6.60 (b, 1H), 6.23 (wt, 1H), 5.24 (w, 1H), 4.3-4.51 (m, 4H), 4.02 (dd, 1H) and 1.45 (s, 9H).

Workup

  1. washwashed with water, 0.5N HCl and Brine
  2. dry with materialThe organic layer was dried over magnesium sulphate
  3. concentrationconcentrated
  4. customtriturated with hexanes (1:3)

Sources & evidence

ORD record
ord-19b1f507b40f420dbff1f3b72bbe0a29
Source dataset
uspto-grants-2011_03
Patent number
US07902401B2

Reaction notes

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