Diisopropylethylamine → (S)-2-[(S)-3-(4-Allyloxy-phenyl)-2-tert-butoxycarbonylamino-propionylamino]-3-methyl-butyric acid methyl ester

HRID 58375

Reaction equation

HRID 58375 reaction equation
[C:1]([NH:8][C@H:9]([C:21]([OH:23])=O)[CH2:10][C:11]1[CH:16]=[CH:15][C:14]([O:17][CH2:18][CH:19]=[CH2:20])=[CH:13][CH:12]=1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.[CH3:49][O:50][C:51](=[O:57])[C@H:52]([CH:54]([CH3:56])[CH3:55])[NH2:53].CCN(C(C)C)C(C)C>CN(C=O)C.CCOC(C)=O>[CH3:49][O:50][C:51](=[O:57])[C@@H:52]([NH:53][C:21](=[O:23])[C@@H:9]([NH:8][C:1]([O:3][C:4]([CH3:5])([CH3:6])[CH3:7])=[O:2])[CH2:10][C:11]1[CH:12]=[CH:13][C:14]([O:17][CH2:18][CH:19]=[CH2:20])=[CH:15][CH:16]=1)[CH:54]([CH3:56])[CH3:55]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 111190Methyl valinate hydrochlorideHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 10853202(2S)-2-{[(tert-butoxy)carbonyl]amino}-3-[4-(prop-2-en-1-yloxy)phenyl]propanoic acid

Product 1

HCID 14632374(S)-2-[(S)-3-(4-Allyloxy-phenyl)-2-tert-butoxycarbonylamino-propionylamino]-3-methyl-butyric acid methyl ester

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

N-BOC-O-allyl-tyrosine (5.0 g, 16.3 mmol), HATU (17.9 mmol) and valine methyl ester hydrochloride (32.6 mmol) were dissolved in anhydrous DMF (25 mL). DIPEA (22.7 mL, 65 mmol) was added and the reaction mixture was stirred at rt for 18 h before being partitioned between EtOAc and 1M hydrochloric acid. The organic phase was then washed sequentially with 1M hydrochloric acid and brine before being dried (MgSO4), filtered and concentrated in vacuo. Purification was achieved using flash chromatography, eluting with a gradient of (50/70) petroleum ether to EtOAc to yield a white solid, 6.08 g, 69%. Rf=0.29 (1/2 EtOAc/(50/70) petroleum ether). m.p. 74-76° C.

Workup

  1. custombefore being partitioned between EtOAc and 1M hydrochloric acid
  2. washThe organic phase was then washed sequentially with 1M hydrochloric acid and brine
  3. dry with materialbefore being dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customPurification
  7. washeluting with a gradient of (50/70) petroleum ether to EtOAc
  8. customto yield a white solid, 6.08 g, 69%

Sources & evidence

ORD record
ord-952aa7f3c11a4c99b1e70d22926fab41
Source dataset
uspto-grants-2016_09
Patent number
US09434762B2

Linked notes

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