HCID 15454947, compound → HCID 15454948, compound

HRID 2287516Notes

Reaction equation

HRID 2287516 reaction equation
C(OC([N:11]1[C@H:15]([CH3:16])[C@H:14]([CH2:17][OH:18])[C@H:13]([NH:19][CH2:20][C:21]2[CH:26]=[C:25]([CH:27]([CH3:29])[CH3:28])[CH:24]=[CH:23][C:22]=2[O:30][CH3:31])[C@@H:12]1[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)=O)C1C=CC=CC=1>[OH-].[OH-].[Pd+2].CO>[OH:18][CH2:17][C@@H:14]1[C@@H:15]([CH3:16])[NH:11][C@@H:12]([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[C@H:13]1[NH:19][CH2:20][C:21]1[CH:26]=[C:25]([CH:27]([CH3:28])[CH3:29])[CH:24]=[CH:23][C:22]=1[O:30][CH3:31]

Participants

4

Reactant 1

HCID 15454947HCID 15454947, compound

Product 1

HCID 15454948HCID 15454948, compoundYield 91.8%

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideCatalyst2×HCID 887MethanolSolvent

Procedure

20% Pd(OH)2 --C (Pearlman's catalyst, Aldrich; 0.44 g) was added to a solution of (2S*,3S*,4R*,5R*)-1-benzyloxycarbonyl-4-hydroxymethyl-3-[N-(5-isopropyl-2-methoxybenzyl)amino]-5-methyl-2-phenylpyrrolidine(0.70 g, 1.36 mmol) and HCO2NH4 (0.51 g, 8.16 mmol) in MeOH (20 ml). The reaction 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. The residue was basified to pH 10 with 1M NaOH aq. solution, and extracted with AcOEt (×4). The combined AcOEt extracts were dried (K2CO3), and concentrated in vacuo to give a pale yellow viscous oil (0.46 g), which crystallized spontaneously on standing in a refrigerator for 2 days. This was recrystallized from AcOEt-n-hexane to give title compound (0.33 g, 63%) as white crystals. The yellow mother liquor was chromatographed over SiO2 (Merck Kieselgel 60, 2.0 g). Elution with CH2Cl2 --MeOH (50:1→20:1) gave an additional amount of title compound (0.06 g, 12%) as a pale yellow viscous oil, which crystallized spontaneously on standing at room temperature; the total yield of title compound amounted to 0.39 g (76%): mp 76.0-78.0 C. (white powders); IRmax (nujol): 3180(w), 1610(w), 1509(s), 1240(s), 1050(m), 800(m), 750(m), 696(m) cm-1 ; 1H-NMR δ: 7.47-7.22(m, 5H), 7.01(dd, J=8.4, 2.2 Hz, 1H), 6.68(d, J=8.4 Hz, 1H), 6.65(d, J=2.2 Hz, 1H), 4.50(d, J=7.7 Hz, 1H), 3.78(dd, J=10.3, 4.3 Hz, 1H), 3.66(dd, J=10.3, 9.4 Hz, 1H), 3.64(s, 3H), 3.61(d,J=12.3 Hz, 1H), 3.47(d,J=12.3 Hz, 1H), 3.39(dd, J=9.7, 7.7 Hz, 1H), 2.92(dq, J=9.4, 6.0 Hz, 1H), 2.76(sep, J=6.8 Hz, 1H), 2.13(br.s, 3H), 1.84(ddd, J=9.4, 9.4, 4.3 Hz, 1H), 1.27(d, J=6.0 Hz, 3H), 1.16(d, J=6.8 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. extractionextracted with AcOEt (×4)
  7. dry with materialThe combined AcOEt extracts were dried (K2CO3)
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-2182ec17d7964e0b98185032ad074434
Source dataset
uspto-grants-2000_07
Patent number
US06083943

Reaction notes

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