Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate → HCID 67485878, compound

HRID 1880573Notes

Reaction equation

HRID 1880573 reaction equation
[F:1][C:2]([F:32])([F:31])[O:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2[CH:11]=[C:12]([O:20][CH2:21][C:22]3[CH:30]=[CH:29][C:25]([C:26](O)=[O:27])=[CH:24][CH:23]=3)[C:13]3[C:18]([CH:19]=2)=[CH:17][CH:16]=[CH:15][CH:14]=3)=[CH:6][CH:5]=1.Cl.[NH2:34][CH2:35][CH2:36][C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38].F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>CN(C=O)C>[F:1][C:2]([F:31])([F:32])[O:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2[CH:11]=[C:12]([O:20][CH2:21][C:22]3[CH:30]=[CH:29][C:25]([C:26]([NH:34][CH2:35][CH2:36][C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])=[O:27])=[CH:24][CH:23]=3)[C:13]3[C:18]([CH:19]=2)=[CH:17][CH:16]=[CH:15][CH:14]=3)=[CH:6][CH:5]=1

Participants

5

Reactant 3

HCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 16218890Tert-butyl 3-aminopropanoate hydrochlorideHCID 67486117HCID 67486117, compound

Product 1

HCID 67485878HCID 67485878, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a DMF solution (2 mL) of the intermediate from Step D (35 mg, 0.08 mmol) was added tert-butyl β-alaninate hydrochloride (30 mg, 0.16 mmol) DIEA (0.06 mL, 0.35 mmol) and BOP (53 mg, 0.12 mmol). The solution was stirred at room temperature for ca. 30 minutes. The solution was then partitioned between ethyl acetate and aqueous 1N HCl. The organic phase was washed with aqueous 1N HCl (3×), brine; dried over MgSO4 and filtered to give tert-butyl N-{4-[({3-[4-(trifluoromethoxy)phenyl]-1-naphthyl}oxy)methyl]benzoyl}-β-alaninate. LCMS1 4.50 min. (M+H)=566. The tert butyl group was removed by treatment with 1/1 DCM/TFA for 1 hour. The crude acid was purified by reverse phase HPLC to give the title compound. 1H NMR (500 MHz, CD3OD): δ 8.57 (s, 1H); 8.31 (d, J=8.1 Hz, 1H); 7.92 (m, 1H); 7.89 (d, J=8.3 Hz, 2H); 7.82 (d, J=8.7 Hz, 2H); 7.70 (m, 3H); 7.56-7.49 (m, 2H); 7.39 (d, J=8.1 Hz, 2H); 7.24 (s, 1H); 5.46 (s, 2H); 3.69-3.65 (m, 2H); 2.68-2.66 (m, 2H). LCMS1 3.97 min. (M+H)=510

Workup

  1. customThe solution was then partitioned between ethyl acetate and aqueous 1N HCl
  2. washThe organic phase was washed with aqueous 1N HCl (3×), brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered

Sources & evidence

ORD record
ord-21bcabf56efd45c5bef23cdf2fe3a47b
Source dataset
uspto-grants-2012_11
Patent number
US08318760B2

Reaction notes

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