(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 1450747Notes

Reaction equation

HRID 1450747 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 crystallizations give 2.6 g of diastereomerically pure 40c. NMR(CDCl3) δ1.40(d,J=6Hz,3H); 1.43(s,9H); 1.60-1.97(m,6H); 3.73(s,3H); 3.74(s,3H); 4.12-4.37 (m, 2H); 4.52-4.61 (m, 1H); 5.12 (bs, 3H); 5.44-5.55 (b s, 1H); 6.73 (b s, 1H); 7.36 (b s, 5H); 13C-NMR: δ18.02(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]D26 -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-31cddb9702734b29b6615b1e7c5e186d
Source dataset
uspto-grants-1997_02
Patent number
US05602275

Reaction notes

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