Diisopropylethylamine → HCID 58960058, compound

HRID 915999Notes

Reaction equation

HRID 915999 reaction equation
[F:1][C:2]([F:15])([F:14])[C@@:3]([OH:13])([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[C:4]([OH:6])=O.[F:16][C:17]1[C:22]([CH2:23][NH2:24])=[CH:21][C:20]([CH3:25])=[CH:19][N:18]=1.C(N(C(C)C)CC)(C)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N2CCCC2)(N2CCCC2)N2CCCC2)C2C=CC=CC=2N=N1>CN(C)C=O>[F:14][C:2]([F:1])([F:15])[C@@:3]([OH:13])([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[C:4]([NH:24][CH2:23][C:22]1[C:17]([F:16])=[N:18][CH:19]=[C:20]([CH3:25])[CH:21]=1)=[O:6]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 11790701HCID 11790701, compoundHCID 534269501-(2-Fluoro-5-methylpyridin-3-yl)methanamine

Product 1

HCID 58960058HCID 58960058, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of (2R)-3,3,3-trifluoro-2-hydroxy-2-phenylpropanoic acid (6-e with R=CF3 and R′=H, 105 mg, 0.48 mmol), the amine (2-e, 67 mg, 0.48 mmol) and diisopropylethylamine (415 uL, 2.4 mmol) in N,N-dimethylformamide (1 mL) was treated at room temperature with benzotriazol-1-yloxytripyrrolidinophosphonium hexafluorophosphate (PyBop, 274 mg, 0.53 mmol). After 14 h, the reaction mixture was partitioned between ethyl acetate and 0.5N—NaOH. The aqueous layer was removed and the organic layer was washed with 0.5N—HCl. The aqueous layer was removed by filtering through a plastic frit. The organic layer was evaporated in vacuo to give the desired product (3-1); HRMS (M+H)=343.1059; 1H NMR (500 MHz, CDCl3) δ 7.89 (bs, 1 H), 7.63 (m, 2H), 7.43 (m, 3 H), 7.39 (d, 1 H, J=7.8 Hz), 6.67 (br, 1 H), 4.72 (m, 1 H), 4.48 (d, 2H, J=6.1 Hz), 2.26 (s, 3 H); compound 3-3 [(2R)-3,3,3-trifluoro-N-(2-fluoro-5-trifluoromethylbenzyl)-2-hydroxy-2-phenylpropanamide] was prepared by the same procedure (2-fluoro-5-trifluoromethylbenzylamine was purchased from Alfa Aesar); HRMS (M+H)=396.0825; 1H NMR (500 MHz, DMSO-6d) δ 8.95 (t, 1 H), 7.95 (s, 1 H), 7.65 (m, 3 H), 7.39 (m, 5 H), 4.40 (dq, 2 H).

Workup

  1. customthe reaction mixture was partitioned between ethyl acetate and 0.5N—NaOH
  2. customThe aqueous layer was removed
  3. washthe organic layer was washed with 0.5N—HCl
  4. customThe aqueous layer was removed
  5. filtrationby filtering through a plastic frit
  6. customThe organic layer was evaporated in vacuo

Sources & evidence

ORD record
ord-1d9d6d5363b94e528b8b8a92e334fb33
Source dataset
uspto-grants-2007_09
Patent number
US07268153B2

Reaction notes

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