(Z)-N-[5,6-Didehydro-N6-[(1,1-dimethylethoxy)-carbonyl]-6-(methoxycarbonyl)-N2-[(phenylmethoxy)-carbonyl]-L-lysyl]-D-alanine Methyl Ester → N-[N6-[(1,1-Dimethylethoxy)carbonyl]-(R)-6-(methoxycarbonyl)-N2-[(phenylmethoxy)carbonyl]-L-lysyl]-D-Alanine Methyl Ester

HRID 1781350Notes

Reaction equation

HRID 1781350 reaction equation
[CH3:1][O:2][C:3](=[O:37])[C@@H:4]([CH3:36])[NH:5][C:6](=[O:35])[C@H:7]([CH2:19][CH2:20]/[CH:21]=[C:22](/[C:31]([O:33][CH3:34])=[O:32])\[NH:23][C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[NH:8][C:9]([O:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)=[O:10].[H][H]>C(O)(=O)C.C1COCC1.Cl([O-])(=O)(=O)=O.[Rh+]>[CH3:1][O:2][C:3](=[O:37])[C@@H:4]([CH3:36])[NH:5][C:6](=[O:35])[C@@H:7]([CH2:19][CH2:20][CH2:21][CH:22]([C:31]([O:33][CH3:34])=[O:32])[NH:23][C:24]([O:26][C:27]([CH3:29])([CH3:30])[CH3:28])=[O:25])[NH:8][C:9]([O:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)=[O:10]

Participants

6

Reactant 2

HCID 86747860(Z)-N-[5,6-Didehydro-N6-[(1,1-dimethylethoxy)-carbonyl]-6-(methoxycarbonyl)-N2-[(phenylmethoxy)-carbonyl]-L-lysyl]-D-alanine Methyl EsterHCID 178418361HCID 178418361, compound

Product 1

HCID 67800369N-[N6-[(1,1-Dimethylethoxy)carbonyl]-(R)-6-(methoxycarbonyl)-N2-[(phenylmethoxy)carbonyl]-L-lysyl]-D-Alanine Methyl EsterYield 92.6%

Reagents, catalysts & solvents 3

HCID 178521653HCID 178521653, compoundCatalystHCID 176Acetic AcidSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 8.5 g of 47c in 25 mL of acetic acid and 250 mL of THF is hydrogenated at 48 psi of hydrogen over 0.5 g of (bicyclo(2.2.1.)hepta-2,5-diene[2S,3S]bis(diphenylphosphino)butane)rhodium(I) perchlorate for 18 h. The reaction is filtered and evaporated to a residue. The residue is chromatographed using variable gradient hexane-ethyl acetate to give 7.9 g of reduced product as a residue. Multiple crystallization give 2.6 g of diastereomerically pure 40c. NMR (CDCl3) δ 1.40 (d, J=6 Hz, 3 H); 1.43 (s, 9 H); 1.60-1.97 (m, 6 H); 3.73 (s, 3 H); 3.74 (s, 3 H); 4.12-4.37 (m, 2 H); 4.52-4.61 (m, 1 H); 5.12 (bs, 3 H); 5.44-5.55 (b s, 1 H); 6.73 (b s, 1 H); 7.36 (b s, 5 H); 13C-NMR: δ 18.02 (CH--CH3); 21.12 (CH2 --CH2 --CH2); 28.23 (--OC(CH3)3); 31.87 (--CH2 --CH2 --); 32.29 (--CH2CH2 --); 47.99 (--CHCH3); 52.23 (--OCH3); 52.38 (--OCH3); 52.75 (OCCHN); 54.41 (OCCHN); 67.01 (--OCH2Ar); 79.97 (--OC(CH3)3); 127.99 (phenyl ring carbon); 128.09 (phenyl ring carbon); 128.44 (ArCH); 136.13 (ArCC); 155.48 (OCONH): 156.23 (OCONH); 171.10 (--CONH--); 173.03 (--CO2 --2X); IR (KBR) (cm-1): 3340(s); 1760(s); 1740(s); 1680(s); 1660(s); 1660(s); 1520(s); MS (FAB) m/z 546 (M+Na)+ ; 524 (MH)+ ; 424 (MH-C4H8CO2)+ ; Anal. Calcd: C, 57.35; H, 7.12; N, 8.03; Found: C, 57.23; H, 7.27; N, 8.03; rotation [α]D25 -9±1; m.p. 120°-121° C.

Workup

  1. customfor 18 h
  2. filtrationThe reaction is filtered
  3. customevaporated to a residue
  4. customThe residue is chromatographed

Sources & evidence

ORD record
ord-c10aac4f4a5d462eb61c169d6e23c1c5
Source dataset
uspto-grants-1997_05
Patent number
US05633280

Reaction notes

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