(2S,4R)-1-tert-Butyl 2-methyl 4-((tert-butyldimethylsilyl)oxy)pyrrolidine-1,2-dicarboxylate → tert-butyl (2S,4R)-4-((tert-butyldimethylsilyl)oxy)-2-(hydroxymethyl)pyrrolidine-1-carboxylate

HRID 2367023Notes

Reaction equation

HRID 2367023 reaction equation
[Si:1]([O:8][C@H:9]1[CH2:13][N:12]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[C@H:11]([C:21](OC)=[O:22])[CH2:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[H-].C([Al+]CC(C)C)C(C)C>C1COCC1.C(OCC)(=O)C.C(C(C(C([O-])=O)O)O)([O-])=O.[K+].[Na+]>[Si:1]([O:8][C@H:9]1[CH2:13][N:12]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[C@H:11]([CH2:21][OH:22])[CH2:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]

Participants

6

Reactant 2

HCID 10618477(2S,4R)-1-tert-Butyl 2-methyl 4-((tert-butyldimethylsilyl)oxy)pyrrolidine-1,2-dicarboxylateHCID 21225700Diisobutylaluminumhydride

Product 1

HCID 11078078tert-butyl (2S,4R)-4-((tert-butyldimethylsilyl)oxy)-2-(hydroxymethyl)pyrrolidine-1-carboxylateYield 106.5%

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 9855836Potassium sodium tartarateSolvent

Conditions

Temperature
-78 °C

Procedure

1-tert-Butyl 2-methyl (2S,4R)-4-{[tert-butyl(dimethyl)silyl]-oxy}pyrrolidine-1,2-dicarboxylate (5.00 g, 13.91 mmol) was dissolved in dry THF (50 mL) under nitrogen and cooled to −78° C. Diisobutylaluminum hydride solution (31.0 mL, 31.0 mmol, 1.0 M in toluene) was added dropwise over 30 minutes. After stirring for ten minutes, the mixture was slowly warmed to room temperature at which point TLC indicated complete conversion. The mixture was diluted with ethyl acetate (200 mL) and saturated aqueous sodium potassium tartrate (200 mL). The mixture was stirred vigorously for 30 minutes until two phases were apparent. The aqueous layer was then extracted twice with ethyl acetate and washed with brine. The organic layer was dried over MgSO4, filtered and concentrated to give 4.91 g of the crude alcohol as a pale yellow oil. LC/MS (M-Boc+H)+ m/z=232.2. 1H NMR (CDCl3) δ 4.88 (d, 1H), 4.27 (bs, 1H), 4.14 (m, 1H), 3.69 (t, 1H), 3.54 (m, 1H), 3.42 (d, 1H), 3.34 (dd, 1H), 1.96 (m, 1H), 1.58 (m, 1H), 1.47 (s, 9H), 0.87 (s, 9H), 0.06 (s, 6H).

Workup

  1. temperaturethe mixture was slowly warmed to room temperature at which point TLC
  2. stirringThe mixture was stirred vigorously for 30 minutes until two phases
  3. extractionThe aqueous layer was then extracted twice with ethyl acetate
  4. washwashed with brine
  5. dry with materialThe organic layer was dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-3cc598180cea43539aef8769369770fa
Source dataset
uspto-grants-2014_04
Patent number
US08697870B2

Reaction notes

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