Diisopropylethylamine → (S)-4-tert-butoxycarbonylamino-4-(4-cyano-benzylcarbamoyl)-butyric acid benzyl ester

HRID 2404000Notes

Reaction equation

HRID 2404000 reaction equation
[NH:1]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[C@H:2]([C:15]([OH:17])=O)[CH2:3][CH2:4][C:5](=[O:14])[O:6][CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.CCN(C(C)C)C(C)C.Cl.[NH2:62][CH2:63][C:64]1[CH:71]=[CH:70][C:67]([C:68]#[N:69])=[CH:66][CH:65]=1>CN(C=O)C.CCOC(C)=O>[CH2:7]([O:6][C:5](=[O:14])[CH2:4][CH2:3][C@H:2]([NH:1][C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[C:15](=[O:17])[NH:69][CH2:68][C:67]1[CH:70]=[CH:71][C:64]([C:63]#[N:62])=[CH:65][CH:66]=1)[C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 83589L-Glutamic acid, N-((1,1-dimethylethoxy)carbonyl)-, 5-(phenylmethyl) esterHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 99422504-(Aminomethyl)benzonitrile hydrochloride

Product 1

HCID 66994809(S)-4-tert-butoxycarbonylamino-4-(4-cyano-benzylcarbamoyl)-butyric acid benzyl ester

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of Boc-Glu(OBzl)-OH (7.08 g, 21.0 mmol), BOP (9.72 g, 22.0 mmol) and DIEA (12.18 ml, 70.0 mmol) in DMF (50 ml) was maintained at room temperature for 20 min, followed by the addition of 4-(aminomethyl)benzonitrile hydrochloride (3.38 g, 20.0 mmol). The reaction mixture was stirred at room temperature for an additional 1 h and diluted with EtOAc (500 ml). The obtained solution was extracted with water (100 ml), 5% aq. NaHCO3 (100 ml) and water (2×100 ml). The organic layer was dried over MgSO4, evaporated and dried in vacuo to provide compound HH (9.65 g, yield exceeded quantitative) as yellowish oil. LC-MS [M+H] 452.0 (C25H29N3O5+H, calc: 452.4). Compound HH was used without further purification.

Workup

  1. extractionThe obtained solution was extracted with water (100 ml), 5% aq. NaHCO3 (100 ml) and water (2×100 ml)
  2. dry with materialThe organic layer was dried over MgSO4
  3. customevaporated
  4. customdried in vacuo
  5. customto provide
  6. customcompound HH (9.65 g, yield exceeded quantitative) as yellowish oil
  7. customCompound HH was used without further purification

Sources & evidence

ORD record
ord-9aea9a8632dd402292fee36daf496f65
Source dataset
uspto-grants-2014_08
Patent number
US08802681B2

Reaction notes

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