121629-14-9|Methyl 4,4-difluorocyclohexanecarboxylate| Ambeed

Size	Price	VIP Price	US Stock	Global Stock	In Stock
{[ item.pr_size ]}		Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate,item.pr_is_large_size_no_price, item.vip_usd) ]}

US Stock: ship in 0-1 business day
Global Stock: ship in 5-7 days

{[ item.pr_size ]}

In Stock

- +

Please Login or Create an Account to: See VIP prices and availability

US Stock: ship in 0-1 business day
Global Stock: ship in 2 weeks

Quality Control of [ 121629-14-9 ] Purity: 98% SDS Specification

COA

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

NMR

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

CNMR

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

HPLC

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

LC-MS

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

1-2 Day Shipping
High Quality
Technical Support

Product Details of [ 121629-14-9 ]

CAS No. :	121629-14-9
Formula :	C₈H₁₂F₂O₂
M.W :	178.17
SMILES Code :	O=C(C1CCC(F)(F)CC1)OC
MDL No. :	MFCD11040454

Safety of [ 121629-14-9 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H302-H315-H319-H335
Precautionary Statements:	P261-P264-P270-P271-P280-P301+P312-P302+P352-P304+P340-P305+P351+P338-P312-P321-P330-P332+P313-P337+P313-P362-P403+P233-P405-P501

Application In Synthesis of [ 121629-14-9 ]

* 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 [ 121629-14-9 ]

[ 121629-14-9 ] Synthesis Path-Downstream 1~35

Yield	Reaction Conditions	Operation in experiment
		EXAMPLE 5 Dehydrohalogenation of 1,1-difluoro-4-carbomethoxy-cyclohexane STR21 A mixture of 1.2 parts of 1,1-difluoro-4-carbomethoxy-cyclohexane and 4.8 parts of o-dichlorobenzene was added to a bed of 10 parts of 2% palladium on carbon at 280 C. A nitrogen gas purge at 280 C. swept the products into cold traps held at 0 C. and -80 C. to yield 4.2 parts of a mixture, consisting of 76% unreacted starting material, 19% 1-fluoro-4-carbomethoxy-cyclohexene and 5% methyl-4-fluorobenzoate, excluding the solvent.

2
[ 121629-14-9 ]
[ 178312-48-6 ]

Yield	Reaction Conditions	Operation in experiment
81%	With lithium aluminium tetrahydride; In tetrahydrofuran; diethyl ether; at 0 - 20℃; for 1h;Inert atmosphere;	Under nitrogen atmosphere, at 0 C, to a suspension of LiA1H4 (2.0 M THF solution,11.2 mL, 22.47 mmol) in dry Et20 (55 mL), <strong>[121629-14-9]methyl 4,4-difluorocyclohexane carboxylate</strong> (1.0 g,5.62 mmol) in dry Et20 (10 mL) was added dropwise. The resulting reaction mixture was stirredat r.t. for 1 h, and then cooled to 0 C. H20 (1.0 mL) was slowly and cautiously added, followedby 3.0 M KOH solution (1.0 mL) and additional H20 (4.5 mL). The mixture was stirred at 0 Cfor 1 h and then filtered off. The organic layer was dried over Na2SO4, filtered and concentrated to dryness, affording the title compound (0.68 g, 81%), which was used in the next step without any further purification. ‘H NMR (DMSO-d6): ö 4.51 (t, 1H, J= 5.6 Hz), 3.26 (t, 2H, J= 7.5 Hz), 2.05-1.93 (m, 2H), 1.86-1.66 (m, 4H), 1.55-1.41 (m, 1H), 1.21-1.08 (m, 2H).
81%		Under nitrogen atmosphere, at 0 C, to a suspension of LiAlH4 (2.0 M THF solution, 11.2 mL, 22.47mmol) in dry Et2O (55 mL), <strong>[121629-14-9]methyl 4,4-difluorocyclohexane carboxylate</strong> (1.0 g, 5.62 mmol) in dryEt2O (10 mL) was added dropwise. The resulting reaction mixture was stirred at room temperature for1 h, and then cooled to 0 C. H2O (1.0 mL) was slowly and cautiously added, followed by 3.0 M KOHsolution (1.0 mL) and additional H2O (4.5 mL). The mixture was stirred at 0 C for 1 h and thenfiltered off. The organic layer was dried over Na2SO4, filtered and concentrated to dryness, affordingthe title compound (0.68 g, 81%), which was used in the next step without any further purification. 1HNMR (DMSO-d6): δ 4.51 (t, 1H, J = 5.6 Hz), 3.26 (t, 2H, J = 7.5 Hz), 2.05-1.93 (m, 2H), 1.86-1.66(m, 4H), 1.55-1.41 (m, 1H), 1.21-1.08 (m, 2H).
77%	With lithium aluminium tetrahydride; In tetrahydrofuran; at 0℃; for 18h;Inert atmosphere;	4,4-Difluoro-cyclohexanecarboxylate (500 mg, 2.60 mmol) was dissolved in tetrahydrofuran (15 mL), and lithium aluminum hydride (1.48 g, 3.90 mmol) was added in batches at 0C, and stirred to react for 18 hours under nitrogen atmosphere. The reaction solution was cooled to 0C and water (1.50 mL), 15% sodium hydroxide (1.50 mL) and water (4.50 mL) were added successively slowly. The solution was filtered, and the filtrate was concentrated under reduced pressure to give the product (4,4-difluoro-cyclohexyl)methanol (300 mg, as a colorless liquid) with a yield of 77%. 1H NMR: (400 MHz,CDCl3) δ 3.58-3.44(m, 2H), 2.20-2.05(m, 2H), 1.93-1.42(m, 6H), 1.40-1.20(m, 2H). MS-ESI calcd. [M + H]+ 151, found 151.

71.55%	With lithium aluminium tetrahydride; In tetrahydrofuran; at 0 - 20℃; for 2h;Inert atmosphere;	Under protection of nitrogen gas, LiAlH4 (2.9 g, 76.32 mmol) was added slowly into a solution of methyl 4,4-difluorocyclohexanecarboxylate (3.40 g, 19.08 mmol) in tetrahydrofuran (40 mL) at 0C, and then the reaction solution was stirred at 20C for 2h. The reaction solution was quenched with water (50 mL) and 1 mol/L sodium hydroxide solution (20 mL), and then filtered. The filtrate was extracted with ethyl acetate (50 mL * 2). The combined organic phase was washed with brine (50 mL), dried over anhydrous sodium sulfate, filtered and evaporated. The residue was purified by column chromatography to give the title compound (yellow oil, 2.05 g, yield of 71.55%). 1H NMR (400MHz, CHLOROFORM-d) δ = 3.53 (d, J=6.5 Hz, 2H), 2.21 - 2.07 (m, 2H), 1.86 (br d, J=13.6 Hz, 2H), 1.81 - 1.64 (m, 2H), 1.58 (br d, J=3.5 Hz, 1H), 1.43 - 1.27 (m, 3H).
	With sodium tetrahydroborate; lithium chloride; In tetrahydrofuran; ethanol; at 0 - 20℃;	Intermediate 56: 2-(4,4-Difluorocyclohexyl)ethyl 4-methylbenzenesulfonate; 2-(4,4-Difluorocyclohexyl)ethyl 4-methylbenzenesulfonate was prepared by following a six-step sequence of straightforward transformation well known in the art: 1) reduction using NaBH4/LiCl, 2) oxidation using Dess-Martin periodinane, 3) Wittg reaction using methoxytriphenylphosphonium chloride, 4) hydrolysis of the resulting enolether with TsOH, 5) reduction using NaBH4, and 6) tosylation of the resulting alcohol; 1H NMR (CDCl3) δ 7.79 (d, J = 8.4 Hz, 2H), 7.36 (d, J = 8.2 Hz, 2H), 4.07 (t, J = 6.0 Hz, 2H), 2.40 (s, 3H), 2.08-1.98 (m, 2H), 1.82-1.42 (m, 7H), 1.27-1.16 (m, 2H); LC-MS [M+Na]+ 341.1

References: [1]Patent: WO2014/144836,2014,A2 .Location in patent: Paragraph 0986; 0987; 0993; 0994.
[2]European Journal of Medicinal Chemistry,2016,vol. 111,p. 138 - 159.
[3]Patent: EP3299371,2018,A1 .Location in patent: Paragraph 0096; 0097; 0098.
[4]Patent: EP3418282,2018,A1 .Location in patent: Paragraph 0300-0301.
[5]Patent: WO2009/65035,2009,A1 .Location in patent: Page/Page column 81-82.

3
[ 121629-14-9 ]
[ 74-88-4 ]
[ 1360568-90-6 ]

Yield	Reaction Conditions	Operation in experiment
		Step 2: Synthesis of methyl 4,4-difluoro-l-methylcyclohexanecarboxylate:To a solution of diisopropylamine (11 ml) in tetrahydrafuran (50 ml), n-BuLi (26 ml) was added at 0 C and the reaction mixture was allowed to stir at same temperature for about 10-15 minutes. The reaction mixture was stirred at room temperature for about 45 minutes. Methyl 4,4-difluorocyclohexanecarboxylate (step 1, 5.3 g) in tetrahydrafuran (40 ml) was added drop-wise to above mixture at -78 C. The reaction mixture was stirred at same temperature for about 2 hours and then methyl iodide was added drop-wise. The reaction was maintained at -78 C for an hour and allowed to attain room temperature. Reaction mixture was stirred overnight at room temperature and quenched at 0 C with saturated aq. NH4C1 solution and the compound was extracted with ethyl acetate. The organic layer was washed with saturated brine solution, dried over anhydrous Na2S04 and concentrated then crude product was directly used for the next step. 1H NMR (CDC13, 300 MHz): δ 3.71 (s, 3H), 2.20- 2.16 (m, 2H), 1.96- 1.71 (m, 4H), 1.57- 1.47 (m, 2H), 1.22 (s, 3H).

References: [1]Patent: WO2012/25857,2012,A1 .Location in patent: Page/Page column 45.

4
[ 122665-97-8 ]
[ 67-56-1 ]
[ 121629-14-9 ]

Yield	Reaction Conditions	Operation in experiment
90.82%	With sulfuric acid; at 0 - 70℃; for 16h;	Concentrated sulfuric acid (2.09 g, 21.32 mmol) was slowly added dropwise to a solution of 4,4-difluorocyclohexylcarbamic acid (7 g, 42.64 mmol) in methanol (70 mL) at 0C, and the reaction solution was stirred at 70C for 16h. The reaction solution was adjusted to pH = 7 with a saturated sodium hydrogen carbonate solution, and extracted with ethyl acetate (100 mL * 2). The combined organic phase was washed with brine (100 mL), dried over anhydrous sodium sulfate, filtered and evaporated. The residue was purified by column chromatography to give the title compound (yellow oil, 6.90 g, yield of 90.82%). 1H NMR (400MHz, CHLOROFORM-d) δ = 3.70 (s, 2H), 2.48 - 2.37 (m, 1H), 2.16 - 2.06 (m, 2H), 2.03 - 1.94 (m, 2H), 1.92 - 1.69 (m, 4H).
	sulfuric acid; for 16h;Reflux;	Step 1: Synthesis of methyl 4,4-difluorocyclohexanecarboxylate:eCone. H2S04 was added drop-wise to a solution of 4,4- difluorocyclohexanecarboxylic acid (6 g) in MeOH (50 ml) at 0 C and the reaction mixture was refluxed for about 16 hours. After the completion of reaction, the solvent was removed and the reaction mixture was dissolved in dichloromethane. The organic layer was washed with saturated NaHC03 solution and the organic layer was dried over anhydrous sodium sulphate. The solvent was removed over rotary evaporator without vacuum to give the crude compound (7.4 g) which was used directly for the next step. 1H NMR (CDC13, 300 MHz): δ 3.69 (s, 3H), 2.42 (m, 1H), 2.10- 1.97 (m, 4H), 1.91- 1.72 (m, 4H).

References: [1]Patent: EP3418282,2018,A1 .Location in patent: Paragraph 0298-0299.
[2]Patent: WO2012/25857,2012,A1 .Location in patent: Page/Page column 44-45.

5
[ 121629-14-9 ]
[ 1360569-34-1 ]