Trifluoroacetic acid → Azetidin-3-ylmethyl (2-amino-5-(thiophen-2-yl)phenyl)carbamate

HRID 2201681Notes

Reaction equation

HRID 2201681 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:9][CH:10]=[CH:11][CH:12]=2)=[CH:4][C:3]=1[NH:13][C:14]([O:16][CH2:17][CH:18]1[CH2:21][N:20](C(OC(C)(C)C)=O)[CH2:19]1)=[O:15].C(O)(C(F)(F)F)=O>ClCCl>[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:9][CH:10]=[CH:11][CH:12]=2)=[CH:4][C:3]=1[NH:13][C:14](=[O:15])[O:16][CH2:17][CH:18]1[CH2:21][NH:20][CH2:19]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86712522Tert-butyl 3-((((2-amino-5-(thiophen-2-yl)phenyl)carbamoyl)oxy)methyl)azetidine-1-carboxylate

Product 1

HCID 86712521Azetidin-3-ylmethyl (2-amino-5-(thiophen-2-yl)phenyl)carbamateYield 55%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl 3-((((2-amino-5-(thiophen-2-yl)phenyl)carbamoyl)oxy)methyl)azetidine-1-carboxylate (0.12 g, 0.30 mmol) in dichloromethane (5 mL) was added TFA (1.5 mL) at 0° C. The reaction was then warmed to room temperature and stirred for 2 h. The solvents were then removed under reduced pressure. A saturated solution of sodium bicarbonate was added. The product was extracted with ethyl acetate, washed with water and brine. The combined organic layers were dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude solid was washed with ether to obtain azetidin-3-ylmethyl (2-amino-5-(thiophen-2-yl)phenyl)carbamate (49.6 mg, 55% yield). ESI+ MS: m/z 304 ([M+H]+), 1H NMR (500 MHz, d6-DMSO): δ 8.78 (bs, 1H), 7.53 (bs, 1H), 7.34 (d, J=4.5 Hz, 1H), 7.22-7.16 (m, 2H), 7.04 (dd, J=5.5; 4.0 Hz, 1H), 6.76-6.70 (m, 1H), 5.18 (bs, 2H), 4.23 (d, J=6.0 Hz, 2H), 3.92 (t, J=8.5 Hz, 2H), 3.70-3.64 (m, 2H), 3.08-3.00 (m, 1H).

Workup

  1. customThe solvents were then removed under reduced pressure
  2. additionA saturated solution of sodium bicarbonate was added
  3. extractionThe product was extracted with ethyl acetate
  4. washwashed with water and brine
  5. dry with materialThe combined organic layers were dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. washThe crude solid was washed with ether

Sources & evidence

ORD record
ord-63dce42ae4ae476aa1537072a258b9a6
Source dataset
uspto-grants-2016_06
Patent number
US09365498B2

Reaction notes

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