Sodium Hydroxide → HCID 15454930, compound

HRID 2287533Notes

Reaction equation

HRID 2287533 reaction equation
C(OC([N:11]1[CH2:16][C@@H:15]([CH2:17][OH:18])[CH2:14][C@H:13]([NH:19][CH2:20][C:21]2[CH:26]=[C:25]([O:27][C:28]([F:31])([F:30])[F:29])[CH:24]=[CH:23][C:22]=2[O:32][CH3:33])[C@@H:12]1[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)=O)C1C=CC=CC=1.[OH-].[Na+]>CO.[OH-].[OH-].[Pd+2]>[OH:18][CH2:17][C@@H:15]1[CH2:16][NH:11][C@@H:12]([C:34]2[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=2)[C@@H:13]([NH:19][CH2:20][C:21]2[CH:26]=[C:25]([O:27][C:28]([F:29])([F:30])[F:31])[CH:24]=[CH:23][C:22]=2[O:32][CH3:33])[CH2:14]1

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 15454928HCID 15454928, compound

Product 1

HCID 15454930HCID 15454930, compoundYield 102.1%

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideCatalystHCID 887MethanolSolvent

Procedure

To a solution of (2S*,3S*,5S*)-1-benzyloxycarbonyl-5-hydroxymethyl-3-[-N-(2-methoxy-5-trifluoromethoxybenzyl)amino]-2-phenylpiperidine (0.545 g, 1.00 mmol) and HCO2NH4 (0.252 g, 4.00 mmol) in MeOH (15.0 ml) was added 20% Pd(OH)2 /C (0.159 g) in one portion. The mixture was stirred and heated at reflux for 30 minutes. The catalyst was filtered off by the aid of Celite, and washed with MeOH. The combined filtrate and washings were concentrated in vacuo to give a yellow syrupy residue, which was basified with IM NaOH aq. solution. The mixture was extracted CH2Cl2, and the combined CH2Cl2 extracts were dried (Na2SO4), and concentrated in vacuo to give a pale yellow oil (0.419 g). This was flash chromatographed over SiO2 (Merck Kieselgel 60, 4.0 g). Elution with CH2Cl2 --MeOH (30:1/20:1) gave title compound (0.380 g, 92.7%) as a yellow oil. IRmax (film): 3320(br., s), 1608(m), 1498(s), 1487(s), 1230(br., s), 1160(br., s), 1030(s), 810(m), 740(m), 700(s) cm-1 ; 1H-NMR δ: 7.40-7.20(m, 5H), 6.99(dd, J=8.8, 2.9 Hz, 1H), 6.85(d, J=2.9 Hz, 1H), 6.63(d, J=8.8 Hz, 1H), 3.86(d, J=2.2 Hz, 1H), 3.64(d, J=14.5 Hz, 1H), 3.60-3.47(m, 2H), 3.50(s, 3H), 3.46-3.36(m, 1H), 3.38(d, J=14.5 Hz, 1H), 2.92-2.84(m, 1H), 2.54(dd, J=1.5, 11.5 Hz, 1H), 2.28-2.10(m, 1H), 2.12(dm, J=12.9 Hz, 1H), 1.69(br.s, 3H; NH×2+OH), 1.35(ddd, J=12.9, 12.9, 2.8 Hz, 1H) ppm.

Workup

  1. temperatureheated
  2. temperatureat reflux for 30 minutes
  3. filtrationThe catalyst was filtered off by the aid of Celite
  4. washwashed with MeOH
  5. concentrationThe combined filtrate and washings were concentrated in vacuo
  6. customto give a yellow syrupy residue, which
  7. extractionThe mixture was extracted CH2Cl2
  8. dry with materialthe combined CH2Cl2 extracts were dried (Na2SO4)
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-6bf0d794a00c407993c6b5449db33ec5
Source dataset
uspto-grants-2000_07
Patent number
US06083943

Reaction notes

Loading…