Citric Acid → Tert-butyl 4-[tert-butyl(dimethyl)silyl]oxy-3-(hydroxymethyl)piperidine-1-carboxylate

HRID 57543Notes

Reaction equation

HRID 57543 reaction equation
[Si:1]([O:8][CH:9]1[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:11][CH:10]1[C:22](OC)=[O:23])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[Li+].[BH4-].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C1COCC1>[Si:1]([O:8][CH:9]1[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:11][CH:10]1[CH2:22][OH:23])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 311Citric AcidHCID 4148881Lithium borohydrideHCID 711134171-O-tert-butyl 3-O-methyl 4-[tert-butyl(dimethyl)silyl]oxypiperidine-1,3-dicarboxylate

Product 1

HCID 71113418Tert-butyl 4-[tert-butyl(dimethyl)silyl]oxy-3-(hydroxymethyl)piperidine-1-carboxylateYield 100%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 1-tert-butyl 3-methyl 4-(tert-butyldimethylsilyloxy)piperidine-1,3 dicarboxylate from step A in THF (100 mL) was cooled at 0° C. and then LiBH4 (1.10 g, 50 mmol) was added in. After stirring for 2 hours as the solution was warmed to room temperature, the pH value was adjusted to 4 with 1M citric acid. After removal of the volatiles in vacuo, the product was extracted in ethyl acetate, washed with water and brine, dried over anhydrous sodium sulfate. Upon filtering and removal of the volatiles in vacuo, tert-butyl 4-(tert-butyldimethylsilyloxy)-3 (hydroxymethyl)piperidine-1-carboxylate was obtained (8.82 g, 100% yield), which was used directly in the next step. MS (m/z): 246 (M-Boc+H)+.

Workup

  1. customAfter removal of the volatiles in vacuo
  2. extractionthe product was extracted in ethyl acetate
  3. washwashed with water and brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationUpon filtering
  6. customremoval of the volatiles in vacuo

Sources & evidence

ORD record
ord-c29da90c7750449689897d9c8517d72b
Source dataset
uspto-grants-2016_09
Patent number
US09434726B2

Reaction notes

Loading…