Ammonia → HCID 59371494, compound

HRID 2095330Notes

Reaction equation

HRID 2095330 reaction equation
FC(F)(F)C(O)=O.[CH2:8]([O:15][C:16]([N:18]1[CH2:21][CH2:20][C@H:19]1[CH2:22][O:23][C:24]1[CH:25]=[C:26]([C:30]2[CH:31]=[C:32]([CH:42]=[CH:43][CH:44]=2)[CH2:33][NH:34]C(=O)OC(C)(C)C)[CH:27]=[N:28][CH:29]=1)=[O:17])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.C([O-])(O)=O.[Na+].CCOC(C)=O.N>C(Cl)Cl.C(Cl)Cl.CO.CCOC(C)=O.O>[CH2:8]([O:15][C:16]([N:18]1[CH2:21][CH2:20][C@H:19]1[CH2:22][O:23][C:24]1[CH:25]=[C:26]([C:30]2[CH:31]=[C:32]([CH:42]=[CH:43][CH:44]=2)[CH2:33][NH2:34])[CH:27]=[N:28][CH:29]=1)=[O:17])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1

Participants

9

Reactant 4

HCID 222AmmoniaHCID 6422Trifluoroacetic acidHCID 59371468HCID 59371468, compoundHCID 86584982Sodium bicarbonate ethyl acetate

Product 1

HCID 59371494HCID 59371494, compoundYield 288.5%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolventHCID 21226129Dichloromethane methanolSolvent

Procedure

In a 100 mL round-bottom flask, a mixture of trifluoroacetic acid (1.2 mL) and water (0.12 mL) was added to a solution of tert-butyl 3-[5-[[1-(benzyloxycarbonyl)-2(S)-azetidinyl]methoxy]-3-pyridyl]benzylcarbamate (329 mg, 653 μmol) in CH2Cl2 (6 mL). The flask was loosely stoppered, and the mixture was stirred magnetically for 7 h. Shortly before, a small aliquot was worked up with aq. NaHCO3/EtOAc and analyzed by TLC (UV detection; SiO2, EtOAc: Rf 0; SiO2, CH2Cl2/MeOH/conc. aq. NH3 87:13:3: Rf approx. 0.55), indicating complete conversion of the starting material. The mixture was evaporated (40° C./14 torr) to obtain a colorless glass (0.76 g), which was taken up in MeOH (3 mL). The pH was adjusted to approx. 8-9 (indicator paper) by adding a few drops of conc. NH3, and the solution was evaporated again. The residue was chromatographed on SiO2 (20×1.9 cm, CH2Cl2/MeOH/conc. aq. NH3 87:13:3), and the product-containing fractions were evaporated and dried (40° C./oil pump) to obtain 262 mg (99.5%) of the free primary amine as a slightly yellowish glass. 1H NMR (CDCl3, 500 MHz) δ 8.50 (s, 1H), 8.32 (br, 1H), 7.56 (s, 1H), 7.51-7.45 (m, 2H), approx. 7.43 (br and overlapping, 1H), 7.40 (m, 1H), 7.32 (br s, 5H), 5.13, 5.08 (ABq, 2H, J=12.3 Hz), 4.67 (m, 1H), approx. 4.5 (br, 1H), 4.22 (br s, 1H), 4.09-4.00 (m, 2H), 3.99 (s, 2H), 2.51-2.37 (m, 2H), 1.64 (br, NH2 and H2O). MS (EI) m/z 403 (M+, 5.8%), 312 (6.4%), 200 (5.4%), 199 (4.0%), 91 (100%).

Workup

  1. customThe mixture was evaporated (40° C./14 torr)

Sources & evidence

ORD record
ord-026ecf67aab94d83bf64878c57595468
Source dataset
uspto-grants-2013_05
Patent number
US08445684B2

Reaction notes

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