Tetrahydrofuran → 8-(N-Cbz-amino)-3-hydroxy-1-(4,4'-dimethoxytrityloxy)octane

HRID 51986Notes

Reaction equation

HRID 51986 reaction equation
[C:1]([NH:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH:17]([OH:21])[CH2:18][CH2:19][OH:20])([O:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:2].C(N(C(C)C)CC)(C)C.[CH3:31][O:32][C:33]1(OC)[CH:52]=[CH:51][C:36]([C:37](Cl)([C:44]2[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=2)[C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)=[CH:35][CH2:34]1.[O:55]1CCC[CH2:56]1>N1C=CC=CC=1.CN(C)C1C=CN=CC=1>[C:1]([NH:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH:17]([OH:21])[CH2:18][CH2:19][O:20][C:37]([C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1)([C:38]1[CH:39]=[CH:40][C:41]([O:55][CH3:56])=[CH:42][CH:43]=1)[C:36]1[CH:51]=[CH:52][C:33]([O:32][CH3:31])=[CH:34][CH:35]=1)([O:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:2]

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 81531DiisopropylethylamineHCID 199627228-(N-Cbz-amino)-1,3-octanediolHCID 534461344,4-Dimethoxytrityl chloride

Product 1

HCID 193543688-(N-Cbz-amino)-3-hydroxy-1-(4,4'-dimethoxytrityloxy)octane

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 1049PyridineSolvent

Procedure

8-(N-Cbz-amino)-1,3-octanediol (4, 25 g, 85 mmoles ) was dissolved in anhydrous pyridine (200 mL), evaporated in vacuo and redissolved in anhydrous pyridine (200 mL). Diisopropylethylamine (38.1 mL, 88 mmoles) and 4-dimethylaminopyridine (170 mg) were added. The mixture was stirred under nitrogen and cooled in an ice bath while adding 4,4-dimethoxytrityl chloride (30 g, 88 mmoles) in tetrahydrofuran (200 mL) dropwise over 1.5 hours. Stirring was continued for 15 minutes after the addition was complete. The mixture was evaporated in vacuo and purified by column chromatography on silica gel, eluting with 20:80:1 ethyl acetate:cyclohexane:triethylamine, then 50:50:1 ethyl acetate:cyclohexane:triethylamine and finally, 100:1 ethyl acetate:triethylamine. Evaporation of the appropriate fractions gave 8-(N-Cbz-amino)-3-hydroxy-1-(4,4'-dimethoxytrityloxy)octane (44 g) as a crisp foam. Mass Spectrum: (M+K)+ @m/z 636. 8-(N-Cbz-amino)-3-hydroxy-1-(4,4'-dimethoxytrityloxy)octane (28.4 g, 47.6 mmoles) was dissolved in methanol (200 mL) and hydrogenated over 10% palladium on carbon (2.84 g) @45 psi hydrogen for 2.5 hours. After filtration and evaporation in vacuo there remained 8-(N-Cbz-amino)-1,3-octanediol (21.5 g). Mass Spectrum: (M+K)+ @m/z 502.

Workup

  1. customevaporated in vacuo
  2. dissolutionredissolved in anhydrous pyridine (200 mL)
  3. temperaturecooled in an ice bath
  4. stirringStirring
  5. additionafter the addition
  6. customThe mixture was evaporated in vacuo
  7. custompurified by column chromatography on silica gel
  8. washeluting with 20:80:1 ethyl acetate
  9. customEvaporation of the appropriate fractions

Sources & evidence

ORD record
ord-ff9dfad60ccf46b1998d960b8313e594
Source dataset
uspto-grants-1997_04
Patent number
US05616505

Reaction notes

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