4-Methylmorpholine → (R)-3-mercapto-2-[(S)-2-methyl-3-trityloxy-propionylamino]-propionic acid methyl ester

HRID 234211Notes

Reaction equation

HRID 234211 reaction equation
[C:1]([O:20][C@@H](C)C(O)=O)([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[CH3:27][O:28][C:29](=[O:34])[C@H:30]([CH2:32][SH:33])[NH2:31].Cl.CN(C)[CH2:38][CH2:39][CH2:40]N=C=NCC.CN1CC[O:51][CH2:50]C1>C(#N)C>[CH3:27][O:28][C:29](=[O:34])[C@@H:30]([NH:31][C:50](=[O:51])[C@@H:39]([CH3:38])[CH2:40][O:20][C:1]([C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)([C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1)[C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1)[CH2:32][SH:33]

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 2733208L-Cysteine, methyl ester, hydrochlorideHCID 54161083(S)-2-trityloxypropionic acid

Product 1

HCID 54008528(R)-3-mercapto-2-[(S)-2-methyl-3-trityloxy-propionylamino]-propionic acid methyl esterYield 16.5%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

To a suspension of 9.97 g of (S)-2-trityloxy-propionic acid, 5.60 g of L-cysteine methyl ester hydrochloride and 6.6 g of N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride in 50 ml acetonitrile was added over 10 min a solution of 6.9 g of 4-methyl-morpholine in 50 ml of acetonitrile. The mixture was stirred at room temperature for 3 h and then partitioned between water and ethyl acetate. The organic layer was washed with brine, dried over magnesium sulfate and evaporated in vacuo. The residue was chromatographed on silica gel using ethyl acetate/hexane (1:2, v/v) as eluent to yield 2.30 g of (R)-3-mercapto-2-[(S)-2-methyl-3-trityloxy-propionylamino]-propionic acid methyl ester as amorphous solid. 1H-NMR (250 MHz,DMSO-d6): δ0.88(d,J=10 Hz,3H); 2.42(t,J=15 Hz, 1H); 2.78 (dd,J=10 Hz and 15 Hz,2H); 3.66(s,3H); 4.01(q,J=10 Hz, 1H); 4.20-4.30(m, 1H); 7.25-7.50(m, 16H); 7.82(d,J=16 Hz,1H) ppm.

Workup

  1. custompartitioned between water and ethyl acetate
  2. washThe organic layer was washed with brine
  3. dry with materialdried over magnesium sulfate
  4. customevaporated in vacuo
  5. customThe residue was chromatographed on silica gel

Sources & evidence

ORD record
ord-e0c84cc91f1d439183e58be7b2c7be11
Source dataset
uspto-grants-1997_01
Patent number
US05594135

Reaction notes

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