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Chemical Structure| 38401-41-1 Chemical Structure| 38401-41-1

Structure of 38401-41-1

Chemical Structure| 38401-41-1

(1-Methylcyclobutyl)methanol

CAS No.: 38401-41-1

4.5 *For Research Use Only !

Cat. No.: A433386 Purity: 97%

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Product Details of [ 38401-41-1 ]

CAS No. :38401-41-1
Formula : C6H12O
M.W : 100.16
SMILES Code : OCC1(C)CCC1
MDL No. :MFCD18072623

Safety of [ 38401-41-1 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H225-H315-H319-H335
Precautionary Statements:P210-P240-P241-P242-P243-P261-P264-P271-P280-P302+P352-P303+P361+P353-P304+P340-P305+P351+P338-P312-P332+P313-P337+P313-P362-P370+P378-P403+P233-P403+P235-P405-P501
Class:3
UN#:1987
Packing Group:

Application In Synthesis of [ 38401-41-1 ]

* 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 [ 38401-41-1 ]

[ 38401-41-1 ] Synthesis Path-Downstream   1~1

  • 1
  • [ 65338-28-5 ]
  • [ 38401-41-1 ]
YieldReaction ConditionsOperation in experiment
1-Methyl-cyclobutanecarboxylic acid ethyl ester 1 (1eq) was stirred under a nitrogen atmosphere at O0C in anhydrous THF. To this solution was added portionwise lithium aluminium hydride (1.5eq) and the suspension was stirred at EPO <DP n="59"/>room temperature for 3 hours. The reaction mixture was cooled on ice, treated with 1 M HCI (aq) and stirred at O0C 20 minutes. The solution was passed through a pad of celite and the filtrate extracted into diethyl ether. The organic phases were dried over MgSO4, filtered and concentrated in vacuo to give (1- methyl-cyclobutyl)-methanol, 2.
With lithium aluminium tetrahydride; In tetrahydrofuran; at 0 - 20℃; for 3h; Example 5 Preparation of 1-methylcvclobutylalanine building block: 1-Methyl-cyclobutanecarboxylic acid ethyl ester 1 was prepared from ethyl cyclobutanecarboxylate by the method described in J. Am. Chem. Soc, Vol. 103 No.2 1981 436-442.1-Methyl-cyclobutanecarboxylic acid ethyl ester 1 (1eq) was stirred under a nitrogen atmosphere at O0C in anhydrous THF. To this solution was added portionwise lithium aluminium hydride (1.5eq) and the suspension was stirred at room temperature for 3 hours. The reaction mixture was cooled on ice, treated with 1 M HCI (aq) and stirred at O0C 20 minutes. The solution was passed through a pad of celite and the filtrate extracted into diethyl ether. The organic phases were dried over MgSO4, filtered and concentrated in vacuo to give (1 -methyl- cyclobutyl)-methanol, 2.Pyridinium chlorochromate (1.25eq) and the same weight of celite were taken up as a suspension in anhydrous dichloromethane. To this was added dropwise a solution of compound 2 (1eq) in anhydrous dichloromethane and the resulting heterogeneous mixture was stirred at room temperature for 3 hours. The reaction mixture was passed through a pad of silica, eluting with 19:1 isohexanes: ethyl acetate to give 1-methylcyclobutanecarboxaldehyde, 3.Compound 3 (1eq) was dissolved with stirring in anhydrous dichloromethane, and to this was added Boc-phosphoglycine trimethyl ester (0.5eq) and 1 ,8-diazabicyclo[5.4.0]undec-7-ene (1.2eq). The resulting solution was stirred at ambient temperature under nitrogen overnight. The reaction mixture was partitioned between dichloromethane and successively 1M HCI (aq), sat. NaHCO3 (aq) and sat. NaCI (aq). The organic layer was dried over MgSO4, filtered and concentrated in vacuo. The resulting oil was purified by flash column chromatography, eluting EPO <DP n="42"/>with 1%methanol in dichloromethane to give 2-tert-butoxycarbonylamino-3-(1-methyl- cyclobutyl)-acrylic acid methyl ester, 4.Compound 4 was dissolved in anhydrous methanol and degassed with nitrogen. (+)-1 ,2-bis (2S,5S)-diethylphosphonolanbenzene (cyclooctadiene)rhodium (I) triflate was added and degassing was continued for a further 10 minutes. The reaction was shaken under a hydrogen atmosphere (4 bar) for 48 hours. The solution was concentrated, in vacuo and purified by flash chromatography, eluting with dichloromethane, to give 2S-tert-butoxycarbonylamino-3-(1- methyl-cyclobutyl)-propionic acid methyl ester, 5.HPLC retention time 5.88min (monitored at 215 and 254 nm) HPLC using Synergy Max RP 80 mum 50x4.6mm column, 10?90% 6 min gradient of solution B (solution A = 0.1 % TFA in water and solution B = 10% A in acetonitrile) at flow rate of 2ml/min.MS [M+H]+ 272.08 (20%) [M-Boc+H]+ 172.06 (100%)Electrospray ionisation, eluting with acetonitrile / ammonium formate buffer.1H NMR (400 MHz, CDCI3) delta 4.89-4.79 (1H, m) 4.33-4.27 (1H, m) 3.71 (3H, s) 1.98-1.62 (8H, m) 1.42 (9H, s) 1.22 (3H, s)
1-Methyl-cyclobutanecarboxylic acid ethyl ester 1 was prepared from ethyl cyclobutanecarboxylate by the method described in J. Am. Chem. Soc, Vol. 103 No.2 1981 436-442.1-Methyl-cyclobutanecarboxylic acid ethyl ester 1 (1eq) was stirred under a nitrogen atmosphere at O0C in anhydrous THF. To this solution was added portionwise lithium aluminium hydride (1.5eq) and the suspension was stirred at room temperature for 3 hours. The reaction mixture was cooled on ice, treated with 1 M HCI (aq) and stirred at O0C 20 minutes. The solution was passed through a pad of celite and the filtrate extracted into diethyl ether. The organic phases were dried over MgSO4, filtered and concentrated in vacuo to give (i-methyl-cyclobutyl)-methanol, 2.Pyridinium chlorochromate (1.25eq) and the same weight of celite were taken up as a suspension in anhydrous dichloromethane. To this was added dropwise a solution of compound 2 (1eq) in anhydrous dichloromethane and the resulting heterogeneous mixture was stirred at room temperature for 3 hours. The reaction mixture was passed through a pad of silica, eluting with 19:1 isohexanes: ethyl acetate to give 1- methylcyclobutanecarboxaldehyde, 3.Compound 3 (1eq) was dissolved with stirring in anhydrous dichloromethane, and to this was added Boc-phosphoglycine trimethyl ester (0.5eq) and 1 ,8- EPO <DP n="120"/>diazabicyclo[5.4.0]undec-7-ene (1.2eq). The resulting solution was stirred at ambient temperature under nitrogen overnight. The reaction mixture was partitioned between dichloromethane and successively 1 M HCI (aq), sat. NaHCO3 (aq) and sat. NaCI (aq). The organic layer was dried over MgSO4, filtered and concentrated in vacuo. The resulting oil was purified by flash column chromatography, eluting with 1%methanol in dichloromethane to give 2-tert-butoxycarbonylamino-3-(1-methyl-cyclobutyl)-acrylic acid methyl ester, 4.Compound 4 was dissolved in anhydrous methanol and degassed with nitrogen. (+)- 1 ,2-bis (2S,5S)-diethylphosphonolanbenzene (cyclooctadiene)rhodium (I) triflate was added and degassing was continued for a further 10 minutes. The reaction was shaken under a hydrogen atmosphere (4 bar) for 48 hours. The solution was concentrated, in vacuo and purified by flash chromatography, eluting with dichloromethane, to give 2S- tert-butoxycarbonylamino-3-(1-methyl-cyclobutyl)-propionic acid methyl ester, 5.HPLC retention time 5.88min (monitored at 215 and 254 nm) HPLC using Synergy Max RP 80 mum 50x4.6mm column, 10?90% 6 min gradient of solution B (solution A = 0.1% TFA in water and solution B = 10% A in acetonitrile) at flow rate of 2ml/min.MS [M+H]+ 272.08 (20%) [M-Boc+H]+ 172.06 (100%)Electrospray ionisation, eluting with acetonitrile / ammonium formate buffer.1H NMR (400 MHz, CDCI35 4.83.79 (1 H, m) 4.33-4.27 (1 H, m) 3.71 (3H, s) 1.98-1.62 (8H, m) 1.42 (9H, s) 1.22 (3H, s)
With lithium aluminium tetrahydride; In diethyl ether; at 0℃; for 2h; Formation of (l-methylcyclobutyl)methanol (112a)Lithium aluminum hydride (2.1 g, 59.4 mmol) was suspended in ether (150 mL) and cooled to 0 C. A solution of <strong>[65338-28-5]ethyl 1-methylcyclobutanecarboxylate</strong>, 111a, (13.0 g, 91.4 mmol) in ether (60 mL) was added dropwise to the LiAlH4 suspension. The mixture was stirred 2 hours in an ice bath then quenched slowly with IN HC1. The layers were separated and the aqueous layer was washed with ether. The combined organic layers were washed with brine and the volatiles were removed with a gentle stream of nitrogen to afford the desired product that was used without further purification: 1H NMR (400 MHz, CDC13) delta 3.54 - 3.39 (m, 4H), 1.99 - 1.74 (m, 8H), 1.74 - 1.62 (m, 4H), 1.46 - 1.18 (m, 3H), 1.13 (d, J = 1.7 Hz, 6H).
With lithium aluminium tetrahydride; In diethyl ether; at 0℃; for 2h; Formation of (l-methylcyclobutyl)methanol (23a) Lithium aluminum hydride (2.1 g, 59.4 mmol) was suspended in ether (150 mL) and cooled to 0 C. A solution of <strong>[65338-28-5]ethyl 1-methylcyclobutanecarboxylate</strong>, 22a, (13.0 g, 91.4 mmol) in ether (60 mL) was added dropwise to the LiAlH4 suspension. The mixture was stirred 2 hours in an ice bath then quenched slowly with IN HC1. The layers were separated and the aqueous layer was washed with ether. The combined organic layers were washed with brine and the volatiles were removed with a gentle stream of nitrogen to afford the desired product that was used without further purification: XH NMR (400 MHz, CDCI3) delta 3.54 - 3.39 (m, 4H), 1.99 - 1.74 (m, 8H), 1.74 - 1.62 (m, 4H), 1.46 - 1.18 (m, 3H), 1.13 (d, J = 1.7 Hz, 6H) ppm.

 

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