Lithium Hydroxide → TFA Cysteine 4-amino-3-methoxybenzoyl methionine

HRID 356084Notes

Reaction equation

HRID 356084 reaction equation
C([NH:8][C@H:9]([C:31]([OH:33])=[O:32])[CH2:10][S:11]C(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)(OC(C)(C)C)=O.C[O:35][C:36](=[O:54])[C@H:37]([CH2:50][CH2:51][S:52][CH3:53])[NH:38][C:39](=[O:49])[C:40]1[CH:45]=[CH:44][C:43]([NH2:46])=[C:42]([O:47][CH3:48])[CH:41]=1.[Li+].[OH-].[SiH](CC)(CC)CC.[C:64]([OH:70])([C:66]([F:69])([F:68])[F:67])=[O:65].Cl.N[C@H](C(O)=O)CS.NC1C=CC(C(N[C@H](C(O)=O)CCSC)=O)=CC=1>C(Cl)Cl.O>[C:64]([OH:70])([C:66]([F:69])([F:68])[F:67])=[O:65].[NH2:8][C@H:9]([C:31]([OH:33])=[O:32])[CH2:10][SH:11].[NH2:46][C:43]1[CH:44]=[CH:45][C:40]([C:39]([NH:38][C@H:37]([C:36]([OH:54])=[O:35])[CH2:50][CH2:51][S:52][CH3:53])=[O:49])=[CH:41][C:42]=1[O:47][CH3:48]

Participants

8

Reactant 5

HCID 3939Lithium HydroxideHCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 67601241N-BOC-S-trityl-cysteine 4-amino-3-methoxybenzoyl methionine methyl esterHCID 86753318HCl cysteine 4-aminobenzoyl methionine

Product 1

HCID 86753316TFA Cysteine 4-amino-3-methoxybenzoyl methionine

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6344DichloromethaneSolvent

Procedure

N-BOC-S-trityl-cysteine-4-amino-3- methoxybenzoyl methionine methyl ester (0.18 g, 0.24 mmol) was deprotected with LiOH at room temperature as described above to give the free acid. The free acid was then further deprotected in CH2Cl2 (1.2 ml) with Et3SiH (0.04 ml, 0.24 mmol) and TFA (1.2 ml). The product was worked up as described for HCl-cysteine-4-aminobenzoyl methionine in Example 1, and HPLC revealed that the product was impure. The crude material was then purified on the HPLC using 0.1% TFA in water and acetonitrile as eluting solvents to result in two pure samples that were expected to be diastereomers. The major component (determined according to the major compound in the HPLC trace) was characterized as follows. mp sub 109° C., decomp 191°-193° C.; [α]25D =-30.0° (c=1, H2O), [α]25D =+19.0° (c=1, H2O); 1H NMR (CD3OD) 2.10 (3 H, s), 2.12-2.18 (1 H, m), 2.20-2.32 (1 H, m), 2.53-2.71 (2 H, m), 3.00 (1 H, dd, J=14.6, 7.5), 3.15 (1 H, dd, J=14.58, 4.8), 4.77 (1 H, dd, J=7.5, 4.8), 7.50 (1 H, d, J=8.4 Hz), 7.56 (1 H, s), 8.23 (1 H, d, J=8.4 Hz); 13C NMR (CD3OD) 15.20, 26.65, 31.60, 31.76, 53.27, 56.58, 56.76, 111.04, 121.08, 122.14, 130.85, 131.85, 150.88, 167.21, 169.61, 175.36; m/ z (FAB) for free amine, 402 (M+1).

Workup

  1. customto give the free acid
  2. customThe crude material was then purified on the HPLC
  3. washas eluting solvents
  4. customto result in two pure samples that
  5. custommp sub 109° C., decomp 191°-193° C.

Sources & evidence

ORD record
ord-ad11bfc31e3a4c109302c524983929dc
Source dataset
uspto-grants-1998_11
Patent number
US05834434

Reaction notes

Loading…