HCID 15454942, compound → HCID 15454943, compound

HRID 2287512Notes

Reaction equation

HRID 2287512 reaction equation
C(OC([N:11]1[C@H:15]([CH3:16])[C@H:14]([CH2:17][O:18][CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[C@H:13]([NH:26][CH2:27][C:28]2[CH:33]=[C:32]([CH:34]([CH3:36])[CH3:35])[CH:31]=[CH:30][C:29]=2[O:37][CH3:38])[C@@H:12]1[C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1)=O)C1C=CC=CC=1>[OH-].[OH-].[Pd+2].CO>[CH2:19]([O:18][CH2:17][C@@H:14]1[C@@H:15]([CH3:16])[NH:11][C@@H:12]([C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)[C@H:13]1[NH:26][CH2:27][C:28]1[CH:33]=[C:32]([CH:34]([CH3:35])[CH3:36])[CH:31]=[CH:30][C:29]=1[O:37][CH3:38])[C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1

Participants

4

Reactant 1

HCID 15454942HCID 15454942, compound

Product 1

HCID 15454943HCID 15454943, compoundYield 99.5%

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideCatalyst2×HCID 887MethanolSolvent

Procedure

20% Pd(OH)2 --C (Pearlman's catalyst, Aldrich; 0.33 g) was added to a solution of (2S*,3S*,4R*,5R*)-1-benzyloxycarbonyl-4-benzyloxymethyl-3-[N-(5-isopropyl-2-methoxybenzyl)amino]-5-methyl-2-phenylpyrrolidine(0.61 g,1.03 mmol) and HCO2NH4 (0.39 g, 6.18 mmol) in MeOH (20 ml). The mixture was stirred and heated at a gentle reflux for 30 minutes. The catalysts were filtered off by the aid of a Celite pad, and washed with MeOH. The combined filtrate and washings were concentrated in vacuo. To the residue was added 1M NaOH aq. solution until the mixture became basic (pH 10-11). This was extracted with CH2Cl2 (×4). The combined CH2Cl2 extracts were washed with sat. NaCl aq. solution (×1), dried (K2CO3), and concentrated in vacuo to give a pale yellow oil (0.47 g). This was chromatographed over SiO2 (Merck Kieselgel 60, 7.0 g). Elution with CH2Cl2 --MeOH (300:1→200:1→100→60:1→50:1) gave title compound (0.40 g, 85%) as a pale yellow viscous oil: IRmax (film): 3340(w), 1610(m), 1498(s), 1250(s), 1110(s), 810(m), 738(s), 700(s) cm1 ; 1H-NMR δ: 7.43-7.20(m, 10H), 7.01(dd, J=8.4, 2.2 Hz, 1H), 6.82(d, J=2.2 Hz, 1H), 6.65(d, J=8.4 Hz, 1H), 4.56(s, 2H), 4.20(d, J=5.5 Hz, 1H), 3.67(d, J=13.6 Hz, 1H), 3.493(dd, J=9.3, 6.2 Hz, 1H), 3,489(s, 3H), 3.57(dd, J=9.3, 6.4 Hz, 1H), 3.42(d, J=13.6 Hz, 1H), 3.13(dd, J=5.5, 2.6 Hz, 1H), 3.06(dq, J=6.2, 6.2 Hz, 1H), 2.74(sep, J=7.0 Hz, 1H), 2.17-1.85(m, 3H), 1.42(d, J=6.2 Hz, 3H), 1.16(d, J=7.0 Hz, 6H) ppm.

Workup

  1. temperatureheated at
  2. temperaturea gentle reflux for 30 minutes
  3. filtrationThe catalysts were filtered off by the aid of a Celite pad
  4. washwashed with MeOH
  5. concentrationThe combined filtrate and washings were concentrated in vacuo
  6. additionTo the residue was added 1M NaOH aq. solution until the mixture
  7. extractionThis was extracted with CH2Cl2 (×4)
  8. washThe combined CH2Cl2 extracts were washed with sat. NaCl aq. solution (×1)
  9. dry with materialdried (K2CO3)
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-e418a9a0e6654ece82958e6753da3530
Source dataset
uspto-grants-2000_07
Patent number
US06083943

Reaction notes

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