Phosphate → HCID 10172022, compound

HRID 1620898Notes

Reaction equation

HRID 1620898 reaction equation
[F:1][C:2]([F:20])([F:19])[CH:3]([NH:10][C@H:11]([C:16]([OH:18])=O)[CH2:12][CH:13]([CH3:15])[CH3:14])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.Cl.[NH2:22][CH2:23][C:24]#[N:25].C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C.P([O-])([O-])([O-])=O>CN(C=O)C>[C:23]([CH2:24][NH:25][C:16](=[O:18])[C@H:11]([CH2:12][CH:13]([CH3:14])[CH3:15])[NH:10][CH:3]([C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1)[C:2]([F:1])([F:20])[F:19])#[N:22]

Participants

7

Reactant 5

HCID 1061PhosphateHCID 8471TriethylamineHCID 2724699PyBOPHCID 11491918Aminoacetonitrile hydrochlorideHCID 57446944N-(2,2,2-Trifluoro-1-phenylethyl)-L-leucine

Product 1

HCID 10172022HCID 10172022, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of N-(2,2,2-trifluoro-1-phenylethyl)-L-leucine (149 mg, 0.50 mmol), aminoacetonitrile hydrochloride (102 mg, 1.1 mmol) and PyBOP (260 mg, 0.50 mmol) was dissolved in DMF (5 mL). Triethylamine (0.3 mL, 2.1 mmol) was added and the mixture was stirred overnight, then poured into pH 3 phosphate buffer and extracted with 3:1 ether/ethyl acetate. The organic phase was washed with saturated aqueous NaHCO3 and brine, dried over MgSO4 and evaporated. Purification by ISCO column chromatography (gradient 20% to 50% ethyl acetate/hexanes) provided N1-(cyanomethyl)-N2-(2,2,2-trifluoro-1-phenylethyl)-L-leucinamide as a 1:1 mixture of diastereomers. MS (+APCI): 313.9 [M+1].

Workup

  1. extractionextracted with 3:1 ether/ethyl acetate
  2. washThe organic phase was washed with saturated aqueous NaHCO3 and brine
  3. dry with materialdried over MgSO4
  4. customevaporated
  5. customPurification by ISCO column chromatography (gradient 20% to 50% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-1cb6653990fe4f5fb8c3d0dc9acc2b8f
Source dataset
uspto-grants-2014_07
Patent number
US08772336B2

Reaction notes

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