Diisopropylethylamine → HCID 58960058, compound

HRID 2358322Notes

Reaction equation

HRID 2358322 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 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, 2 H), 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, 2 H, 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-d6) 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 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-06679451f6d34d2eaa8f1ac08a44ce9c
Source dataset
uspto-grants-2010_07
Patent number
US07763659B2

Reaction notes

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