Sodium Bicarbonate → tert-Butyl 1-(1-hydroxyprop-1-yl)-2-(tert-butyldimethylsilyloxy)-8-azaspiro[4.5]decane-8-carboxylate

HRID 8763

Reaction equation

HRID 8763 reaction equation
[CH:1]([CH:3]1[C:7]2([CH2:12][CH2:11][N:10]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:9][CH2:8]2)[CH2:6][CH2:5][CH:4]1[O:20][Si:21]([C:24]([CH3:27])([CH3:26])[CH3:25])([CH3:23])[CH3:22])=[O:2].[CH2:28]([Mg]Br)[CH3:29].C(=O)(O)[O-].[Na+]>C1COCC1.CCOCC>[OH:2][CH:1]([CH:3]1[C:7]2([CH2:12][CH2:11][N:10]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:9][CH2:8]2)[CH2:6][CH2:5][CH:4]1[O:20][Si:21]([C:24]([CH3:27])([CH3:26])[CH3:25])([CH3:22])[CH3:23])[CH2:28][CH3:29]

Participants

6

Reactant 3

HCID 516892Sodium BicarbonateHCID 21983956tert-Butyl 1-formyl-2-(tert-butyldimethylsilyloxy)-8-azaspiro[4.5]decane-8-carboxylateHCID 178418443HCID 178418443, compound2×

Product 1

HCID 21983938tert-Butyl 1-(1-hydroxyprop-1-yl)-2-(tert-butyldimethylsilyloxy)-8-azaspiro[4.5]decane-8-carboxylateYield 81.2%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of tert-butyl 1-formyl-2-(tert-butyldimethylsilyloxy)-8-azaspiro[4.5]decane-8-carboxylate (0.284 g, 0.714 mmol) from Step C in THF (7 mL) was cooled to −70° C. and ethyl magnesium bromide (3.0M, 0.262 mL, 0.786 mmol) was added. The reaction was stirred for 30 min and then an additional aliquot of ethyl magnesium bromide (3.0M, 0.050 mL, 0.142 mmol) was added. After 5 min, the reaction was diluted with ether, poured into sodium bicarbonate, and extracted three times with ether. The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated. The residue was purified by flash chromatography eluting with 10 to 20% ethyl acetate in hexanes to afford the title compound (0.248 g) as a mixture of isomers. MS/EI (acetonitrile/water): m/z 354 (100%, M+1–74 (t-BuOH)), 372 (M+1–56 (C4H8); 428 (M+1); retention time=4.29 min.

Workup

  1. waitAfter 5 min
  2. extractionextracted three times with ether
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by flash chromatography
  8. washeluting with 10 to 20% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-b6b06fbe021c44f3b8106057062933c8
Source dataset
uspto-grants-2006_08
Patent number
US07091211B2

Linked notes

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