Water → HCID 15454908, compound

HRID 2287528Notes

Reaction equation

HRID 2287528 reaction equation
C[Al](C)C.[NH4+:5].[Cl-].[CH2:7]([O:14][C:15]([N:17]1[CH2:22][C@@H:21]([CH2:23][O:24][Si:25]([C:28]([CH3:31])([CH3:30])[CH3:29])([CH3:27])[CH3:26])[CH2:20][C@H:19]([C:32](OC)=[O:33])[C@@H:18]1[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)=[O:16])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.O>C1(C)C=CC=CC=1>[CH2:7]([O:14][C:15]([N:17]1[CH2:22][C@@H:21]([CH2:23][O:24][Si:25]([C:28]([CH3:31])([CH3:30])[CH3:29])([CH3:27])[CH3:26])[CH2:20][C@H:19]([C:32](=[O:33])[NH2:5])[C@@H:18]1[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)=[O:16])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1

Participants

6

Reactant 4

HCID 962WaterHCID 25517Ammonium Chloride2×HCID 15454906HCID 15454906, compoundHCID 16682925Trimethylaluminum

Product 1

HCID 15454908HCID 15454908, compoundYield 102.2%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent3×

Procedure

Under an atmosphere of N2, a 2.0M solution of Me3Al in PhMe (Aldrich, 140 ml, 280 mmol) was added dropwise to a stirred and ice-cooled suspension of NH4Cl (14.92 g, 279 mmol) in dry PhMe (280 ml). After the addition was complete, the reaction mixture was allowed to stirr at room temperature for 30 minutes; at this point, solid NH4Cl disappeared completely, and the clear, homogeneous mixture resulted. To this was added a solution of (2R*,3S*,5S*)-1-benzyloxycarbonyl-5-(tert-butyldimethylsilyloxy)methyl-3-methoxycarbonyl-2-phenylpiperidine (13.88 g, 27.89 mmol) in dry PhMe (30.0 ml) dropwise at room temperature: on the addition, the reaction mixture became turbid. This was stirred and heated at a bath temperature of 50 C. overnight (ca. 20 hours). The turbid white reaction mixture was ice-cooled; and H2O (80.0 ml, 4.40 mol) was added carefully, wherein H2 gas evolved violently. The resultant white precipitates were filtered off by the aid of Celite, and washed with AcOEt (80 ml×5). The combined filtrate and AcOEt washings were washed with sat. NaCl aq. solution (×2), dried (MgSO4), and concentrated in vacuo to give a viscous colorless oil (13.76 g). This was flash chromatographed over SiO2 (Merck Kieselgel 60, 100 g). Elution with n-hexane-AcOEt (5:1/2:1/1:1) gave title compound (11.10 g, 82.4%) as a colorless syrup. IRmax (film): 3405(s), 3340(s), 3200(s), 3100(w), 3070(m), 3045(m), 1735(m), 1675(br., v.s), 1610(s), 1498(s), 1160(s), 1100(s), 836(s), 775(s), 737(s) cm-1 ; 1H-NMR δ: 7.42-7.18(m, 10H), 5.83(d, J=5.1 Hz, 1H), 5.67(br.s, 1H), 5.47(br.s, 1H), 5.20(d, J=12.5 Hz, 1H), 5.13(d, J=12.5 Hz, 1H), 3.91(br.d, J=13.9 Hz, 1H), 3.63(dd, J=10.0, 6.8 Hz, 1H), 3.53(dd, J=10.0, 7.7 Hz, 1H), 3.08(dd,J=13.9, 7.7 Hz, 1H), 2.98(ddd,J=17.6, 5.1, 4.8 Hz, 1H), 2.25-1.91(m, 3H), 0.87(s, 9H), 0.02(s, 6H) ppm.

Workup

  1. temperatureice-cooled
  2. additionAfter the addition
  3. customthe clear, homogeneous mixture resulted
  4. additionon the addition
  5. stirringThis was stirred
  6. customovernight (ca. 20 hours)
  7. temperaturecooled
  8. customThe resultant white precipitates
  9. filtrationwere filtered off by the aid of Celite
  10. washwashed with AcOEt (80 ml×5)
  11. washThe combined filtrate and AcOEt washings were washed with sat. NaCl aq. solution (×2)
  12. dry with materialdried (MgSO4)
  13. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-6a31b63ac41b4348ae072421b2ea9d11
Source dataset
uspto-grants-2000_07
Patent number
US06083943

Reaction notes

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