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Chemical Structure| 790667-99-1 Chemical Structure| 790667-99-1

Structure of 790667-99-1

Chemical Structure| 790667-99-1

(2S,4S)-tert-Butyl 4-hydroxy-2-methylpiperidine-1-carboxylate

CAS No.: 790667-99-1

4.5 *For Research Use Only !

Cat. No.: A461169 Purity: 98%

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Product Details of [ 790667-99-1 ]

CAS No. :790667-99-1
Formula : C11H21NO3
M.W : 215.29
SMILES Code : O=C(N1[C@@H](C)C[C@@H](O)CC1)OC(C)(C)C
MDL No. :MFCD22415236
InChI Key :RCXJVQLRZJXWNM-IUCAKERBSA-N
Pubchem ID :45097440

Safety of [ 790667-99-1 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P280-P301+P312-P302+P352-P305+P351+P338

Application In Synthesis of [ 790667-99-1 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Downstream synthetic route of [ 790667-99-1 ]

[ 790667-99-1 ] Synthesis Path-Downstream   1~2

  • 1
  • [ 790667-49-1 ]
  • [ 790667-91-3 ]
  • [ 790667-99-1 ]
YieldReaction ConditionsOperation in experiment
30%; 52% With sodium tetrahydroborate; In ethanol; for 2h; Combine 2-METHYL-4-OXO-PIPERIDINE-1-CARBOXYLIC acid tert-butyl ester isomer l (10.0 g, 46.89 mmol), absolute ethanol (200 mL), and sodium borohydride (2.66 g, 70.33 mmol) with stirring. After 2 hr. , concentrate the reaction mixture and then partition the residue between water (100 mL) and 1 : 1 hexane: ethyl acetate (100 mL). Separate the aqueous layer and wash with 1: 1 hexane: ethyl acetate (4X100 mL), combine the organic layers, wash with aqueous NACI solution, dry over sodium sulfate, filter and concentrate. Purify the residue by silica gel flash chromatography eluting with 7: 3 hexane : ethyl acetate to obtain the resolved trans isomer 1 (3.03 g, 30%) and cis isomer 1 (5.2 g, 52%). Trans isomer 1 :'H NMR (CDCl3) : 4.5 (m, 1H), 4.05 (m, 1H), 3.95 (M, 1H), 2.9 (M, 1H), 1.9 (m, 1H), 1.8 (m, 1H), 1.5 (m, 1H), 1.45 (s, 9H), 1.4 (m, 1H), 1.35 (m, 1H), 1.1 (d, 3H). cis isomer 1 :] H NMR (CDC13) : 4.25 (m, 1H), 4.15 (M, 1H), 3.8 (m, 1H), 3.25 (m, 1H), 1.8 (M, 1H), 1.65 (m, 3H), 1. 4 (s, 9H), 1.3 (d, 3H).
41%; 49% With methanol; sodium tetrahydroborate; In tetrahydrofuran; at 0℃; for 1h; General procedure: A flask was charged with t-butyl (3aR,6aS)-5-oxohexahydrocyclopenta[c]pyrrole-2(lH)- carboxylate (1.00 g, 4.44 mmol, 1.00 equiv) and MeOH (15 mL). Sodium borohydride (0.507 g, 13.4 mmol, 3.00 equiv) was added at 0 C. The resulting solution was stirred for 2 h at room temperature and quenched with water (20 mL). The resulting solution was extracted with DCM (3 x 30 mL) and the organic layers were combined, washed with brine (1 x 50 mL), dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to provide 0.950 g (94% yield) of t-butyl tra5-5-hydroxyhexahydrocyclopenta[c]pyrrole-2(lH)-carboxylate as a yellow oil. LCMS (ESI, m/z): 228 [M+H]+.
  • 2
  • [ 790667-49-1 ]
  • [ 790667-99-1 ]
YieldReaction ConditionsOperation in experiment
81% With potassium dihydrogenphosphate; D-glucose; sodium hydrogencarbonate; sodium hydroxide; In water; dimethyl sulfoxide; at 20 - 30℃; for 16.5h;pH 6.9 - 7.0;Large scale; Enzymatic reaction; To a glass-lined reactor containing deionized water (460 L), and potassium dihydrogen phosphate (6.5 kg, 0.41 equiv) at 20 C. is charged DMSO (27.4 kg, 1.0 vol) and D-(+)-glucose monohydrate (28.9 kg, 1.25 equiv). The internal temperature is adjusted to 30 C., and the pH of the reaction is adjusted to 6.9 by addition of aqueous sodium hydroxide (8%, 15 L, 0.28 equiv). The reactor is charged with <strong>[790667-49-1]tert-butyl (2S)-2-methyl-4-oxo-piperidine-1-carboxylate</strong> (24.9 kg, 1.0 equiv (99.1% ee)), and the mixture is agitated at 30 C. for 15 min. Ketoreductase (KRED-130, 250 g, 1% w/w), glucose dehydrogenase (GDH-101, 250 g, 1% w/w), and NADP sodium salt (63 g, 0.25% w/w) are charged directly to the reaction mixture via an open port. The mixture is maintained at a temperature of 30 C. and pH 7.0±0.2 via addition of 8% aqueous NaHCO3. After stirring for 16.5 h (99.5% conversion), the reaction is charged with Celite (12.5 kg, 50 w/w %) and toluene (125 L, 5 vol). After stirring for 30 min at 30 C., the mixture is transferred to another 2000 L reactor via an in-line GAF-filter (4 sock) over the period of 1 h. The mixture is allowed to stand 30 min without agitation, the layers are separated, and the aqueous layer is back-extracted with toluene (2×125 L). The combined organic layers are filtered (in-line GAF-filter), and the toluene mixture is washed with aqueous sodium chloride solution (25%, 125 L, 5 vol) at 25 C. The resulting toluene solution is azeotropically dried (partial vacuum, internal temp <60 C.) to 0.10 w/w % water, and cooled to 20 C. The mixture is filtered out of the reactor via a cartridge filter into clean drums under positive nitrogen pressure. The reaction mixture is then transferred from the drums into a 500 L glass lined vessel and concentrated under vacuum (<60 C.) to a target residual volume of 56 L (2.25 vol). n-Heptane (169 kg, 10 vol) is charged at 40 C., and the mixture is seeded with 25 g of tert-butyl (2S,4S)-4-hydroxy-2-methyl-piperidine-1-carboxylate. The resulting thick slurry is diluted with additional n-heptane (25 L, 1 vol) and cooled to 16 C. over 4 h. The product is isolated via centrifugation, washing with n-heptane (25 L per spin; 4 spins necessary), yielding 20.3 kg (81%; >99.9% ee) after drying for 11 h in a tray dryer at 30 C. ES/MS (m/e) 238 (M+Na).
81% With glucose dehydrogenase; potassium dihydrogenphosphate; D-glucose; ketoreductase; beta-nicotinamideadenine dinucleotide phosphate sodium; sodium hydrogencarbonate; In water; dimethyl sulfoxide; at 30℃; for 16.5h;pH 7;Large scale; Enzymatic reaction; To a glass-lined reactor containing deionized water (460 L), and potassium dihydrogen phosphate (6.5 kg, 0.41 equiv) at 20 C. is charged DMSO (27.4 kg, 1.0 vol) and D-(+)-glucose monohydrate (28.9 kg, 1.25 equiv). The internal temperature is adjusted to 30 C., and the pH of the reaction is adjusted to 6.9 by addition of aqueous sodium hydroxide (8%, 15 L, 0.28 equiv). The reactor is charged with <strong>[790667-49-1]tert-butyl (2S)-2-methyl-4-oxo-piperidine-1-carboxylate</strong> (24.9 kg, 1.0 equiv (99.1% ee)), and the mixture is agitated at 30 C. for 15 min. Ketoreductase (KRED-130, 250 g, 1% w/w), glucose dehydrogenase (GDH-101, 250 g, 1% w/w), and NADP sodium salt (63 g, 0.25% w/w) are charged directly to the reaction mixture via an open port. The mixture is maintained at a temperature of 30 C. and pH 7.0±0.2 via addition of 8% aqueous NaHCO3. After stirring for 16.5 h (99.5% conversion), the reaction is charged with Celite (12.5 kg, 50 w/w %) and toluene (125 L, 5 vol). After stirring for 30 min at 30 C., the mixture is transferred to another 2000 L reactor via an in-line GAF-filter (4 sock) over the period of 1 h. The mixture is allowed to stand 30 min without agitation, the layers are separated, and the aqueous layer is back-extracted with toluene (2×125 L). The combined organic layers are filtered (in-line GAF-filter), and the toluene mixture is washed with aqueous sodium chloride solution (25%, 125 L, 5 vol) at 25 C. The resulting toluene solution is azeotropically dried (partial vacuum, internal temp 99.9% ee) after drying for 11 h in a tray dryer at 30 C. ES/MS (m/e) 238 (M+Na).
81% With potassium dihydrogenphosphate; D-glucose; NADP sodium salt; sodium hydrogencarbonate; sodium hydroxide; In water; dimethyl sulfoxide; at 30℃; for 16.5h;pH 7;Large scale; To a glass-lined reactor containing deionized water (460 L), and potassium dihydrogen phosphate (6.5 kg, 0.41 equiv) at 20 C is charged DMSO (27.4 kg , 1.0 vol) and D-(+)-glucose monohydrate (28.9 kg, 1.25 equiv). The internal temperature is adjusted to 30 C, and the pH of the reaction is adjusted to 6.9 by addition of aqueous sodium hydroxide (8%, 15 L, 0.28 equiv). The reactor is charged with tert-butyl (2S)-2- methyl-4-oxo-piperidine-l-carboxylate (24.9 kg, 1.0 equiv (99. l%ee)), and the mixture is agitated at 30 C for 15 min. Ketoreductase (KRED-130, 250 g, 1% w/w), glucose dehydrogenase (GDH-101, 250 g, 1% w/w), and NADP sodium salt (63 g, 0.25% w/w) are charged directly to the reaction mixture via an open port. The mixture is maintained at a temperature of 30 C and pH 7.0 ± 0.2 via addition of 8% aqueous NaHCO,. After stirring for 16.5 h (99.5% conversion), the reaction is charged with Celite (12.5 kg, 50 w/w%) and toluene (125 L, 5 vol). After stirring for 30 min at 30 C, the mixture is transferred to another 2000 L reactor via an in-line GAF-filter (4 sock) over the period of 1 h. The mixture is allowed to stand 30 min without agitation, the layers are separated, and the aqueous layer is back-extracted with toluene (2 x 125 L). The combined organic layers are filtered (in-line GAF-filter), and the toluene mixture is washed with aqueous sodium chloride solution (25%, 125 L, 5 vol) at 25 C. The resulting toluene solution is azeotropically dried (partial vacuum, internal temp 99.9% ee) after drying for 11 h in a tray dryer at 30 C. ES/MS (m/e) 238 (M+Na).
 

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