There will be a HazMat fee per item when shipping a dangerous goods. The HazMat fee will be charged to your UPS/DHL/FedEx collect account or added to the invoice unless the package is shipped via Ground service. Ship by air in Excepted Quantity (each bottle), which is up to 1g/1mL for class 6.1 packing group I or II, and up to 25g/25ml for all other HazMat items.

Type	HazMat fee for 500 gram (Estimated)
Excepted Quantity	USD 0.00
Limited Quantity	USD 15-60
Inaccessible (Haz class 6.1), Domestic	USD 80+
Inaccessible (Haz class 6.1), International	USD 150+
Accessible (Haz class 3, 4, 5 or 8), Domestic	USD 100+
Accessible (Haz class 3, 4, 5 or 8), International	USD 200+

Structure of 412278-24-1

*Storage: {[sel_prStorage]}

*Shipping: {[sel_prShipping]}

4.5 *For Research Use Only! Not for Human Use. We Do Not Sell to Patients.

{[proInfo.pro_purity]}

Cat. No.: {[proInfo.prAm]} Purity: {[proInfo.pro_purity]}

Change View

Size

Price

VIP Price

DE Stock

US Stock

Asia Stock

Global Stock

In Stock

{[ item.pr_size ]}{[ size_append_text(item.pr_size, proInfo.prAm, 'list') ]}

Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate,item.pr_is_large_size_no_price, item.vip_usd) ]}

{[ item.pr_size ]}
{[ size_append_text(item.pr_size, proInfo.prAm, 'list') ]}

In Stock

- +

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

Quality Control of [ 412278-24-1 ] Purity: 95% 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 [ 412278-24-1 ]

CAS No. :	412278-24-1
Formula :	C₉H₁₇NO₄
M.W :	203.24
SMILES Code :	O=C(OC(C)(C)C)N[C@H]1COC[C@@H]1O
English Name :	tert-Butyl ((3S,4R)-4-hydroxytetrahydrofuran-3-yl)carbamate
MDL No. :	MFCD11617817
InChI Key :	SFIADDJLFYFDGK-BQBZGAKWSA-N
Pubchem ID :	20792948

Safety of [ 412278-24-1 ]

GHS Pictogram:
Signal Word:
Hazard Statements:
Precautionary Statements:
Class:
UN#:
Packing Group:

Application In Synthesis of [ 412278-24-1 ]

* 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 [ 412278-24-1 ]

[ 412278-24-1 ] Synthesis Path-Downstream 1~14

1
[ 412278-24-1 ]
[ 124-63-0 ]
[ 1391732-77-6 ]

Yield	Reaction Conditions	Operation in experiment
96%	With triethylamine In dichloromethane at 0 - 25℃; for 1h; Inert atmosphere;	226.4 Step 4: Intermediate 5, (3R,45)-4-(tert-butoxycarbonylamino)tetrahydrofuran-3- ylmethanesulfonate Step 4: Intermediate 5, (3R,45)-4-(tert-butoxycarbonylamino)tetrahydrofuran-3- ylmethanesulfonate [00733j To the solution of tert-butyl (3S,4R)-4-hydroxytetrahydrofuran-3-yl carbamate (1.20 g, 5.91 mmol) and TEA (0.89 g, 1.50 eq) in DCM (4OmL), was added methanesulfonyl chloride (0.88 g, 1.30 eq), in portions at 0 °C under a nitrogen atmosphere. The mixture was slowly warmed to room temperature and was stirred for 1 h. The resultant solution was washed with water, 1 N HC1, and saturated aqueous sodium bicarbonate, dried over anhydrous Na2SO4 and concentrated under reduced pressure to afford the title compound (1.60 g, 96%). ‘HNMR (CDC13, 400MHz): ö 1.45 (s, 9H), 3.21 (s, 3H), 3.70-3.73 (m, 1H), 3.97-3.99 (m, 1H), 4.05-4.07 (m, 1H), 4.17-4.19 (m, 2H), 4.76 (s, 1H), 5.05 (d, 1H).

References: [1]Current Patent Assignee: BRISTOL MYERS SQUIBB - WO2014/144737, 2014, A1 Location in patent: Paragraph 00733.

2
[ 24424-99-5 ]
[ 190792-70-2 ]
[ 412278-24-1 ]

Yield	Reaction Conditions	Operation in experiment
87%	With triethylamine In methanol at 20℃;	32.1 Step 1. Step 1. tert-butyl ((3S,4R)-4-hydroxytetrahydrofuran-3-yl)carbamate (32-2a) To a stirred solution of (3R,4S)-4-aminotetrahydrofuran-3-ol (32-1a, 482 mg, 4.67 mmol) and di-tert-butyl dicarbonate (1122 mg, 5.14 mmol) in MeOH (10 mL) was added Et3N (1.6 mL, 11.48 mmol) and the resulting mixture was stirred at room temperature until complete consumption of starting material was observed. The reaction mixture was then concentrated to dryness. The crude material was treated with water (6 mL) and the resulting solid was then filtered off and washed with water to afford the desired product 32-2a (838.1 mg, 4.08 mmol, 87% yield) as a white solid. MS [M-tBu+H]+=148.2. 1H NMR (400 MHz, Chloroform-d) δ 4.71 (s, 1H), 4.32 (dq, J=5.7, 2.9 Hz, 1H), 4.10 (ddd, J=16.0, 9.7, 5.6 Hz, 2H), 3.97 (dt, J=6.4, 3.2 Hz, 1H), 3.71 (dd, J=10.0, 3.3 Hz, 1H), 3.63 (dd, J=9.5, 3.4 Hz, 1H), 2.82 (s, 1H), 1.48 (s, 9H).
82%	With triethylamine In methanol at 20℃; for 45h;	1 Step 1: Synthesis of tert-butyl ((3S,4R)-4-hydroxytetrahydrofuran-3-yl)carbamate Intermediate (3R,4S)-4-aminotetrahydrofuran-3-ol was prepared as in WO 01/29013 (PCT/US00/28815; pp. 44-45; Example 1). A solution of (3R,4S)-4-aminotetrahydrofuran-3-ol (10.6 g, 103 mmol), triethylamine (26 g, 257 mmol), and BOC anhydride (24.7 g, 113 mmol) in methanol (206 mL, 0.5 M) was stirred at room temperature over 45 hours. The solvents were then removed under reduced pressure. The beige solid was treated with water (about 120 mL). A white crystalline solid was isolated by filtration and dried overnight under vacuum to yield tert-butyl ((3S,4R)-4-hydroxytetrahydrofuran-3-yl)carbamate as a white solid (17.08 g, 82%).
81%	With triethylamine In methanol at 20℃; for 24h; Cooling with ice;	1 Step 1: Preparation of tert-butyl ((3S,4R)-4-hydroxytetrahydrofuran-3-yl)carbamate (3R,4S)-4-aminotetrahydrofuran-3-ol (5.00 g, 48.487 mmol) was dissolved in methanol (100 mL), then triethylamine (12.24 g, 121.2 mmol) was added, the mixture was cooled under ice water bath, then Boc2O (11.64 g, 53.34 mmol) was added. After the addition, the mixture was stirred at room temperature for 24 h. The reaction was completed, the organic phase was concentrated to remove the majority solvent. Water (100 mL) was added, and the mixture was stirred to precipitate a large amount of white solids. The mixture was filtrated and washed with water to obtain compound tert-butyl ((3S,4R)-4-hydroxytetrahydrofuran-3-yl)carbamate (8.00 g, yield: 81%). 1H NMR (400 MHz, Chloroform-d) δ 4.72 (s, 1H), 4.29 (m, 1H), 4.09 (m, 1H), 4.08 (m, 1H), 3.95 (s, 1H), 3.69 (m, 1H), 3.61 (m, 1H), 1.45 (s, 9H).

64%	With sodium hydroxide In tetrahydrofuran at 20℃; for 2h;	10.2 Step 2: Preparation of compound 10C At room temperature, racemate 10B (4.8 g, 46.5 mmol) was dissolved in tetrahydrofuran (50 mL), followed by the addition of Boc 2O (12.8 mL, 55.8 mmol) and NaOH solution (31 mL, 93 mmol, 3 M), and stirred at room temperature for 2 hours. TLC (PE/EA = 5:1) showed that the starting material disappeared. Ethyl acetate and saturated brine were added to the reaction solution, and the liquid was separated. The aqueous phase was extracted twice with ethyl acetate, and the combined organic phase was washed three times with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated to obtain racemate compound 10C (6.0 g, 64%). The crude product was directly subjected to the next step without purification.
61%	In tetrahydrofuran at 18 - 25℃;	226.3 Step 3: Intermediate 4, tert-butyl (35,4R)-4-hydroxytetrahydrofuran-3-yl carbamate Step 3: Intermediate 4, tert-butyl (35,4R)-4-hydroxytetrahydrofuran-3-yl carbamate [00732j To a solution of (3R,45)-4-aminotetrahydrofuran-3-ol (1.00 g, 9.71 mmol) in THF (30 mL) was added (Boc)20 (2.70 g, 1.30 equiv). The mixture was allowed to stir at ambient temperature overnight. The reaction solution was concentrated under reduced pressure. The residue was partitioned between EtOAc and water, the organic layer was washed with water and brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified by column chromatography (eluting with 5% EtOAc/hexane) to afford the title compound as a white solid (1.20 g, 61%). ‘HNMR (CDC13, 400MHz): ö 1.45 (s, 9H), 3.11 (s, 1H), 3.60-3.63 (m, 1H), 3.68-3.71 (1H), 3.95 (s, br, 1H), 4.04-4.11 (m, 2H), 4.28-4.30 (m, 1H),4.74 (s, br, 1H).
1.8 g	With triethylamine In tetrahydrofuran for 16h;	23-12.2 Triethylamine (6 mL) and di-tert-butyl dicarbonate (9.8 mL) were added to a solution of trans-4-aminotetrahydrofuran-3-ol (2.9 g) obtained in Reference Example 23-12 (1) in tetrahydrofuran (40 mL),followed by stirring for 16 hours. A saturated sodium chloride aqueous solution was added to the reactionmixture, and the resultant product was extracted with ethyl acetate, followed by drying over anhydroussodium sulfate. The solvent was distilled off under reduced pressure, and the obtained residues were purifiedby silica gel column chromatography (hexane:ethyl acetate=10:1→1:9), whereby tert-butyl (trans-4-hydroxytetrahydrofuran-3-yl)carbamate (1.8 g) was obtained
38.78 g	With triethylamine In methanol at 20℃; for 3h;	19C Example 19C Example 19B (23.70 g, 229.83 mmol) was dissolved in 200 ml methanol, into which was added triethyl amine(4.65 g, 45.97 mmol, 6.37 ml), and then dropwise added Boc-anhydride (65.21 g, 298.78 mmol, 68.64 ml), and themixture was reacted at room temperature for 3 hours. When TLC detected that the reaction has been completed, thesolvent was removed by rotatory evaporation, and then 100 ml methyl tert-butyl ether was added, and the mixture wasstirred for 15 minutes. The filter cake after being filtered was the product, which need not to be further purified to give38.78 g Example 19C as a light yellow solid, with a yield of 83.0%. 1HNMR (400 MHz, CHLOROFORM-d) δ 4.78 (br s, 1H), 4.24-4.31 (m, 1H), 3.98-4.13 (m, 2H), 3.94 (br s, 1H),3.66-3.73 (m, 1H), 3.62 (dd, J=2.76, 9.29 Hz, 1H), 1.44 (s, 9H).

References: [1]Current Patent Assignee: NOVARTIS - US2020/17461, 2020, A1 Location in patent: Paragraph 1492-1493.
[2]Current Patent Assignee: BLUEPRINT MEDICINES - US2015/119405, 2015, A1 Location in patent: Paragraph 0232; 0233.
[3]Current Patent Assignee: ABBISKO THERAPEUTICS - US2019/270742, 2019, A1 Location in patent: Paragraph 0322-0324.
[4]Current Patent Assignee: SHANGHAI JIYU PHARMACEUTICAL TECHNOLOGY - WO2023/66292, 2023, A1 Location in patent: Page/Page column 22-23.
[5]Current Patent Assignee: BRISTOL MYERS SQUIBB - WO2014/144737, 2014, A1 Location in patent: Paragraph 00732.
[6]Current Patent Assignee: FUJIFILM - US2016/168139, 2016, A1 Location in patent: Paragraph 1842; 1845; 1846.
[7]Current Patent Assignee: GUANGDONG ZHONGSHENG PHARMACEUTICAL - EP3543227, 2019, A1 Location in patent: Paragraph 0383-0385.

3
[ 412278-24-1 ]
[ 1628794-74-0 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: triethylamine / dichloromethane / 1 h / 0 - 25 °C / Inert atmosphere 2: sodium azide / 1-methyl-pyrrolidin-2-one / 5 h / 95 °C

References: [1]Current Patent Assignee: BRISTOL MYERS SQUIBB - WO2014/144737, 2014, A1.

4
[ 412278-24-1 ]
[ 1628794-75-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: triethylamine / dichloromethane / 1 h / 0 - 25 °C / Inert atmosphere 2: sodium azide / 1-methyl-pyrrolidin-2-one / 5 h / 95 °C 3: 10% Pd/C; hydrogen / methanol / 18 - 25 °C / 2280.15 Torr
	Multi-step reaction with 2 steps 1.1: triphenylphosphine / tetrahydrofuran / 0.17 h / 0 °C 1.2: 1 h / 0 °C 2.1: hydrazine hydrate / ethanol / 2.5 h / 50 - 75 °C
	Multi-step reaction with 2 steps 1: triphenylphosphine; diethylazodicarboxylate / tetrahydrofuran; toluene / 3 h / 60 °C 2: hydrazine hydrate / ethanol / 11.5 h

	Multi-step reaction with 2 steps 1: triphenylphosphine; diethylazodicarboxylate / toluene / 20 - 30 °C / Inert atmosphere 2: ethylenediamine / 2-methyltetrahydrofuran / 25 - 77 °C / Inert atmosphere
	Multi-step reaction with 2 steps 1: diethylazodicarboxylate; triphenylphosphine / tetrahydrofuran / 14 h / 20 °C 2: hydrazine hydrate / ethanol / 1 h / 80 °C
	Multi-step reaction with 2 steps 1: triphenylphosphine; diethylazodicarboxylate / tetrahydrofuran / 1 h / Cooling with ice 2: hydrazine hydrate / ethanol / 2 h / 75 °C

References: [1]Current Patent Assignee: BRISTOL MYERS SQUIBB - WO2014/144737, 2014, A1.
[2]Current Patent Assignee: BLUEPRINT MEDICINES - US2015/119405, 2015, A1.
[3]Current Patent Assignee: FUJIFILM - US2016/168139, 2016, A1.
[4]Weiberth, Franz J.; Bourque, Andre J.; Elenbaas, Steven; Hanna, Reda; Powers, Matthew R.; Siegel, Craig S.; Zhao, Jin [Synthesis, 2017, vol. 49, # 18, p. 4133 - 4136].
[5]Current Patent Assignee: GUANGDONG ZHONGSHENG PHARMACEUTICAL - EP3543227, 2019, A1.
[6]Current Patent Assignee: ABBISKO THERAPEUTICS - US2019/270742, 2019, A1.

5
[ 412278-24-1 ]
[ 1628795-05-0 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: triethylamine / dichloromethane / 1 h / 0 - 25 °C / Inert atmosphere 2: sodium azide / 1-methyl-pyrrolidin-2-one / 5 h / 95 °C 3: 10% Pd/C; hydrogen / methanol / 18 - 25 °C / 2280.15 Torr 4: N-ethyl-N,N-diisopropylamine / 1-methyl-pyrrolidin-2-one / 1 h / 80 °C

References: [1]Current Patent Assignee: BRISTOL MYERS SQUIBB - WO2014/144737, 2014, A1.

6
[ 412278-24-1 ]
[ 1628795-18-5 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: triethylamine / dichloromethane / 1 h / 0 - 25 °C / Inert atmosphere 2: sodium azide / 1-methyl-pyrrolidin-2-one / 5 h / 95 °C 3: 10% Pd/C; hydrogen / methanol / 18 - 25 °C / 2280.15 Torr 4: N-ethyl-N,N-diisopropylamine / 1-methyl-pyrrolidin-2-one / 1 h / 80 °C / Inert atmosphere

References: [1]Current Patent Assignee: BRISTOL MYERS SQUIBB - WO2014/144737, 2014, A1.

7
[ 412278-24-1 ]
[ 1628795-26-5 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: triethylamine / dichloromethane / 1 h / 0 - 25 °C / Inert atmosphere 2: sodium azide / 1-methyl-pyrrolidin-2-one / 5 h / 95 °C 3: 10% Pd/C; hydrogen / methanol / 18 - 25 °C / 2280.15 Torr 4: N-ethyl-N,N-diisopropylamine / 1-methyl-pyrrolidin-2-one / 1 h / 100 °C

References: [1]Current Patent Assignee: BRISTOL MYERS SQUIBB - WO2014/144737, 2014, A1.

8
[ 412278-24-1 ]
[ 1628795-32-3 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: triethylamine / dichloromethane / 1 h / 0 - 25 °C / Inert atmosphere 2: sodium azide / 1-methyl-pyrrolidin-2-one / 5 h / 95 °C 3: 10% Pd/C; hydrogen / methanol / 18 - 25 °C / 2280.15 Torr 4: N-ethyl-N,N-diisopropylamine / 1-methyl-pyrrolidin-2-one / 3 h / 85 °C / Inert atmosphere

References: [1]Current Patent Assignee: BRISTOL MYERS SQUIBB - WO2014/144737, 2014, A1.

9
[ 412278-24-1 ]
[ 1628795-37-8 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: triethylamine / dichloromethane / 1 h / 0 - 25 °C / Inert atmosphere 2: sodium azide / 1-methyl-pyrrolidin-2-one / 5 h / 95 °C 3: 10% Pd/C; hydrogen / methanol / 18 - 25 °C / 2280.15 Torr 4: N-ethyl-N,N-diisopropylamine / 1-methyl-pyrrolidin-2-one / 1.5 h / 85 °C / Inert atmosphere

References: [1]Current Patent Assignee: BRISTOL MYERS SQUIBB - WO2014/144737, 2014, A1.

10
[ 412278-24-1 ]
[ 1628795-47-0 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: triethylamine / dichloromethane / 1 h / 0 - 25 °C / Inert atmosphere 2: sodium azide / 1-methyl-pyrrolidin-2-one / 5 h / 95 °C 3: 10% Pd/C; hydrogen / methanol / 18 - 25 °C / 2280.15 Torr 4: N-ethyl-N,N-diisopropylamine / 1-methyl-pyrrolidin-2-one / 3 h / 85 °C / Inert atmosphere

References: [1]Current Patent Assignee: BRISTOL MYERS SQUIBB - WO2014/144737, 2014, A1.

11
[ 412278-24-1 ]
[ 1628795-65-2 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: triethylamine / dichloromethane / 1 h / 0 - 25 °C / Inert atmosphere 2: sodium azide / 1-methyl-pyrrolidin-2-one / 5 h / 95 °C 3: 10% Pd/C; hydrogen / methanol / 18 - 25 °C / 2280.15 Torr 4: N-ethyl-N,N-diisopropylamine / 1-methyl-pyrrolidin-2-one / 2 h / 85 °C / Inert atmosphere

References: [1]Current Patent Assignee: BRISTOL MYERS SQUIBB - WO2014/144737, 2014, A1.

12
[ 412278-24-1 ]
[ 1628795-71-0 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: triethylamine / dichloromethane / 1 h / 0 - 25 °C / Inert atmosphere 2: sodium azide / 1-methyl-pyrrolidin-2-one / 5 h / 95 °C 3: 10% Pd/C; hydrogen / methanol / 18 - 25 °C / 2280.15 Torr 4: N-ethyl-N,N-diisopropylamine / 1-methyl-pyrrolidin-2-one / 3 h / 80 °C

References: [1]Current Patent Assignee: BRISTOL MYERS SQUIBB - WO2014/144737, 2014, A1.

13
[ 85-41-6 ]
[ 412278-24-1 ]
[ 1707290-09-2 ]

Yield	Reaction Conditions	Operation in experiment
13.16 g	Stage #1: phthalimide; tert-butyl ((3S,4R)-4-hydroxytetrahydrofuran-3-yl)carbamate With triphenylphosphine In tetrahydrofuran at 0℃; for 0.166667h; Stage #2: With di-isopropyl azodicarboxylate In tetrahydrofuran at 0℃; for 1h;	2 Step 2: Synthesis of tert-butyl ((3R,4S)-4-(1,3-dioxoisoindolin-2-yl)tetrahydrofuran-3-yl)carbamate A mixture of tert-butyl ((3S,4R)-4-hydroxytetrahydrofuran-3-yl)carbamate (15.36 g, 76 mmol), phthalimide (13.34 g, 91 mmol), and triphenylphosphine (23.8 g, 91 mmol) was stirred in THF (378 mL, 0.2 M) at 0° C. for 10 minutes before dropwise addition of DIAD (18.34 g, 91 mmol) over 20 minutes. The reaction was stirred about 40 minutes at 0° C. The solvent was removed under reduced pressure, and the crude oil was treated with less than 50 mL of diethyl ether and sonicated. A white precipitate was formed. The solid was isolated by filtration, washed with small amounts of ether, and dried to yield 10.62 g of white solid. The cooled-down filtrate was refiltered to yield additional 2.54 g of white solid for a total yield of 13.16 g of tert-butyl ((3R,4S)-4-(1,3-dioxoisoindolin-2-yl)tetrahydrofuran-3-yl)carbamate
327 mg	With triphenylphosphine; diethylazodicarboxylate In tetrahydrofuran; toluene at 60℃; for 3h;	23-12.3 Triphenylphosphine (780 mg), phthalimide (440 mg), and 2.2 mol/L diethyl azodicarboxylate/toluene (1.3mL) were added to a solution of tert-butyl (trans-4-hydroxytetrahydrofuran-3-yl)carbamate (200 mg)obtained in Reference Example 23-12 (2) in tetrahydrofuran (10 mL), followed by stirring at 60° C. for 3hours. A saturated sodium hydrogen carbonate aqueous solution was added to the reaction mixture, and theresultant product was extracted with ethyl acetate, followed by drying over anhydrous sodium sulfate. Thesolvent was distilled off under reduced pressure, and the obtained residues were purified by silica gel columnchromatography (hexane:ethyl acetate=10:1→2:1), whereby tert-butyl (cis-4-(1,3-dioxoisoindilin-2-yl)tetrahydrofuran-3-yl)carbamate (327 mg) was obtained
	With triphenylphosphine; diethylazodicarboxylate In toluene at 20 - 30℃; Inert atmosphere;	2-[(3S,4R)-4-Aminotetrahydrofuran-3-yl]isoindoline-1,3-dione (4) A 2-L, three-necked flask with a condenser, magnetic stirrer and static N2 bubbler was charged with 8 (124.5 g, 612.6 mmol, 1.0 equiv), phthalimide (135.2 g, 918.9 mmol, 1.5 equiv), triphenylphosphine (241.0 g, 918.9 mmol, 1.5 equiv) and toluene (1.62 L). Diisopropyl azodicarboxylate (180.9 mL, 918.9 mmol, 1.5 equiv) was added to the suspension by using a syringe in 1 h while at 22-30 °C. After stirring an additional 1-3 h at ambient temperature, the mixture was filtered to remove triphenylphosphine oxide and most of the excess phthalimide. The filtrate was washed with 10% w/v aqueous K2CO3 (200 mL),10 water (2 × 200 mL) to pH 7, and brine (75 mL). The toluene phase was partially concentrated over a rotary evaporator to obtain an orange solution of 12 (1.02 kg), which partially crystallized on standing. With stirring, trifluoroacetic acid (656.7 mL, 8.57 mol, 14.0 equiv) was charged over 30-60 min while maintaining 23-33 °C. After stirring for >2 h at 20-25 °C, the solution was partially concentrated over a rotary evaporator (45 °C) to afford 1.1 kg of a solution, which was then chased twice with aliquots of toluene (100-200 mL) to distill excess TFA. The solution was seeded with pure 4 after the second toluene addition. The final toluene suspension (893 g) was diluted with toluene (625 mL) and MTBE (400 mL) and then cooled and stirred at 20 °C for 30 min. After filtration and drying (50 °C), 4 was obtained as a TFA salt as a fine white powder. Yield: 144.2 g (68%) 1H NMR (400 MHz, methanol-d4): δ = 7.91 (m, 2 H), 7.86 (m, 2 H), 5.18 (ddd, J = 9.1, 7.4, 6.6 Hz, 1 H), 4.52 (dd, J = 9.2, 7.5 Hz, 1 H), 4.17-4.05 (m, 4 H). 13C NMR (101 MHz, DMSO-d6): δ = 168.75, 158.9 (q), 134.95, 132.25, 123.56, 117.5 (q), 70.17, 65.97, 52.03, 51.03. HRMS-ESI+: m/z [M + H]+ calcd for C12H13N2O3: 233.09207; found: 233.09181.

85.5 g	With triphenylphosphine; diethylazodicarboxylate In tetrahydrofuran at 20℃; for 14h;	19D Example 19D Example 19C (38.78 g, 190.82 mmol), phthalimide (33.69 g, 228.98 mmol) and triphenylphosphine (60.06 g,228.98 mmol) were dissolved in 500 ml tetrahydrofuran, into which was added diisopropyl azodicarboxylate (46.30 g,228.98 mmol, 44.52 ml), and the mixture was reacted at room temperature for 14 hours. When TLC detected that thereaction has been completed, the solvent was removed by rotatory evaporation, and the mixture was purified over aflash silica gel column (petroleum ether/ethyl acetate=3/1) to give 85.50 g product Example 19D as a white solid. 1HNMR (400 MHz, CHLOROFORM-d) δ 7.85-7.88 (m, 2H), 7.74-7.76 (m, 2H), 4.88 (br d, J=9.54 Hz, 1H),4.44-4.55 (m, 1H), 4.37 (br t, J=8.16 Hz, 1H), 4.12-4.21 (m, 2H), 3.78-3.90 (m, 1H), 1.10 (s, 9H).
	With triphenylphosphine; diethylazodicarboxylate In tetrahydrofuran for 1h; Cooling with ice;	2 Step 2: Preparation of tert-butyl ((3R,4S)-4-(1,3-dicarbonylisoindolin-2-yl)tetrahydrofuran-3-yl)carbamate Tert-butyl ((3S,4R)-4-hydroxyltetrahydrofuran-3-yl)carbamate (200 mg, 0.984 mmol), triphenylphosphine (620 mg, 2.364 mmol) and isoindoline-1,3-dione (173 mg, 1.181 mmol) were dissolved in tetrahydrofuran (10 mL), the mixture was cooled under ice water bath, then diisopropyl azodicarboxylate (717 mg, 3.546 mmol) was slowly added dropwise. After addition, the mixture was stirred under ice water bath for 1 h. The reaction liquid was directly concentrated and separated by column chromatography (Eluent: PE/EA 15-30%) to obtain a crude product compound tert-butyl ((3R,4S)-4-(1,3-dicarbonylisoindolin-2-yl)tetrahydrofuran-3-yl)carbamate (950 mg). 1H NMR (400 MHz, Chloroform-d) δ 7.87 (m, 2H), 7.75 (m, 2H), 4.84 (d, J=9.5 Hz, 1H), 4.51 (t, J=8.0 Hz, 1H), 4.37 (t, J 8.3 Hz, 1H), 4.21-4.15 (m, 1H), 4.09 (t, J 8.8 Hz, 1H), 3.85 (m, J=9.2, 6.4 Hz, 1H), 1.11 (s, 9H). MS m/z (ESI): 559.5 [M+H]+.

References: [1]Current Patent Assignee: BLUEPRINT MEDICINES - US2015/119405, 2015, A1 Location in patent: Paragraph 0232; 0234.
[2]Current Patent Assignee: FUJIFILM - US2016/168139, 2016, A1 Location in patent: Paragraph 1842; 1847; 1848.
[3]Weiberth, Franz J.; Bourque, Andre J.; Elenbaas, Steven; Hanna, Reda; Powers, Matthew R.; Siegel, Craig S.; Zhao, Jin [Synthesis, 2017, vol. 49, # 18, p. 4133 - 4136].
[4]Current Patent Assignee: GUANGDONG ZHONGSHENG PHARMACEUTICAL - EP3543227, 2019, A1 Location in patent: Paragraph 0386-0388.
[5]Current Patent Assignee: ABBISKO THERAPEUTICS - US2019/270742, 2019, A1 Location in patent: Paragraph 0325-0328.

14
[ 412278-24-1 ]
[ 1707289-81-3 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: triphenylphosphine / tetrahydrofuran / 0.17 h / 0 °C 1.2: 1 h / 0 °C 2.1: hydrazine hydrate / ethanol / 2.5 h / 50 - 75 °C 3.1: sodium hydrogencarbonate / 1-methyl-pyrrolidin-2-one / 12 h / 95 °C

References: [1]Current Patent Assignee: BLUEPRINT MEDICINES - US2015/119405, 2015, A1.

Historical Records

Technical Information

• Acyl Group Substitution • Appel Reaction • Bouveault-Blanc Reduction • Buchwald-Hartwig C-N Bond and C-O Bond Formation Reactions • Catalytic Hydrogenation • Chan-Lam Coupling Reaction • Chugaev Reaction • Complex Metal Hydride Reductions • Corey-Kim Oxidation • Dess-Martin Oxidation • Ester Cleavage • Hydride Reductions • Jones Oxidation • Lawesson's Reagent • Leuckart-Wallach Reaction • Mannich Reaction • Martin's Sulfurane Dehydrating Reagent • Mitsunobu Reaction • Moffatt Oxidation • Oxidation of Alcohols by DMSO • Petasis Reaction • Preparation of Alcohols • Preparation of Amines • Reactions of Alcohols • Reactions of Amines • Reactions with Organometallic Reagents • Ritter Reaction • Sharpless Olefin Synthesis • Specialized Acylation Reagents-Carbodiimides and Related Reagents • Specialized Acylation Reagents-Ketenes • Specialized Acylation Reagents-Vilsmeier Reagent • Swern Oxidation • Ugi Reaction

Related Functional Groups of
[ 412278-24-1 ]

Alcohols

A444889 [1430230-65-1]

rel-tert-Butyl ((3R,4S)-4-hydroxytetrahydrofuran-3-yl)carbamate

Similarity: 1.00

A560421 [477584-34-2]

tert-Butyl (4-hydroxytetrahydrofuran-3-yl)carbamate

Similarity: 1.00

A541195 [1631070-69-3]

tert-Butyl ((3R,4R)-rel-4-hydroxytetrahydrofuran-3-yl)carbamate

Similarity: 1.00

Amides

A444889 [1430230-65-1]

rel-tert-Butyl ((3R,4S)-4-hydroxytetrahydrofuran-3-yl)carbamate

Similarity: 1.00

A560421 [477584-34-2]

tert-Butyl (4-hydroxytetrahydrofuran-3-yl)carbamate

Similarity: 1.00

A541195 [1631070-69-3]

tert-Butyl ((3R,4R)-rel-4-hydroxytetrahydrofuran-3-yl)carbamate

Similarity: 1.00

A246620 [1292324-45-8]

(S)-tert-Butyl (tetrahydrofuran-3-yl)carbamate

Similarity: 0.90

A141986 [1292324-51-6]

(R)-tert-Butyl (tetrahydrofuran-3-yl)carbamate

Similarity: 0.90

Amines

A444889 [1430230-65-1]

rel-tert-Butyl ((3R,4S)-4-hydroxytetrahydrofuran-3-yl)carbamate

Similarity: 1.00

A560421 [477584-34-2]

tert-Butyl (4-hydroxytetrahydrofuran-3-yl)carbamate

Similarity: 1.00

A541195 [1631070-69-3]

tert-Butyl ((3R,4R)-rel-4-hydroxytetrahydrofuran-3-yl)carbamate

Similarity: 1.00

A246620 [1292324-45-8]

(S)-tert-Butyl (tetrahydrofuran-3-yl)carbamate

Similarity: 0.90

A141986 [1292324-51-6]

(R)-tert-Butyl (tetrahydrofuran-3-yl)carbamate

Similarity: 0.90

Related Parent Nucleus of
[ 412278-24-1 ]

Tetrahydrofurans

A444889 [1430230-65-1]

rel-tert-Butyl ((3R,4S)-4-hydroxytetrahydrofuran-3-yl)carbamate

Similarity: 1.00

A560421 [477584-34-2]

tert-Butyl (4-hydroxytetrahydrofuran-3-yl)carbamate

Similarity: 1.00

A541195 [1631070-69-3]

tert-Butyl ((3R,4R)-rel-4-hydroxytetrahydrofuran-3-yl)carbamate

Similarity: 1.00

A246620 [1292324-45-8]

(S)-tert-Butyl (tetrahydrofuran-3-yl)carbamate

Similarity: 0.90

A141986 [1292324-51-6]

(R)-tert-Butyl (tetrahydrofuran-3-yl)carbamate

Similarity: 0.90

Precautionary Statements-General
Code	Phrase
P101	If medical advice is needed,have product container or label at hand.
P102	Keep out of reach of children.
P103	Read label before use
Prevention
Code	Phrase
P201	Obtain special instructions before use.
P202	Do not handle until all safety precautions have been read and understood.
P210	Keep away from heat/sparks/open flames/hot surfaces. - No smoking.
P211	Do not spray on an open flame or other ignition source.
P220	Keep/Store away from clothing/combustible materials.
P221	Take any precaution to avoid mixing with combustibles
P222	Do not allow contact with air.
P223	Keep away from any possible contact with water, because of violent reaction and possible flash fire.
P230	Keep wetted
P231	Handle under inert gas.
P232	Protect from moisture.
P233	Keep container tightly closed.
P234	Keep only in original container.
P235	Keep cool
P240	Ground/bond container and receiving equipment.
P241	Use explosion-proof electrical/ventilating/lighting/equipment.
P242	Use only non-sparking tools.
P243	Take precautionary measures against static discharge.
P244	Keep reduction valves free from grease and oil.
P250	Do not subject to grinding/shock/friction.
P251	Pressurized container: Do not pierce or burn, even after use.
P260	Do not breathe dust/fume/gas/mist/vapours/spray.
P261	Avoid breathing dust/fume/gas/mist/vapours/spray.
P262	Do not get in eyes, on skin, or on clothing.
P263	Avoid contact during pregnancy/while nursing.
P264	Wash hands thoroughly after handling.
P265	Wash skin thouroughly after handling.
P270	Do not eat, drink or smoke when using this product.
P271	Use only outdoors or in a well-ventilated area.
P272	Contaminated work clothing should not be allowed out of the workplace.
P273	Avoid release to the environment.
P280	Wear protective gloves/protective clothing/eye protection/face protection.
P281	Use personal protective equipment as required.
P282	Wear cold insulating gloves/face shield/eye protection.
P283	Wear fire/flame resistant/retardant clothing.
P284	Wear respiratory protection.
P285	In case of inadequate ventilation wear respiratory protection.
P231 + P232	Handle under inert gas. Protect from moisture.
P235 + P410	Keep cool. Protect from sunlight.
Response
Code	Phrase
P301	IF SWALLOWED:
P304	IF INHALED:
P305	IF IN EYES:
P306	IF ON CLOTHING:
P307	IF exposed:
P308	IF exposed or concerned:
P309	IF exposed or if you feel unwell:
P310	Immediately call a POISON CENTER or doctor/physician.
P311	Call a POISON CENTER or doctor/physician.
P312	Call a POISON CENTER or doctor/physician if you feel unwell.
P313	Get medical advice/attention.
P314	Get medical advice/attention if you feel unwell.
P315	Get immediate medical advice/attention.
P320
P302 + P352	IF ON SKIN: wash with plenty of soap and water.
P321
P322
P330	Rinse mouth.
P331	Do NOT induce vomiting.
P332	IF SKIN irritation occurs:
P333	If skin irritation or rash occurs:
P334	Immerse in cool water/wrap n wet bandages.
P335	Brush off loose particles from skin.
P336	Thaw frosted parts with lukewarm water. Do not rub affected area.
P337	If eye irritation persists:
P338	Remove contact lenses, if present and easy to do. Continue rinsing.
P340	Remove victim to fresh air and keep at rest in a position comfortable for breathing.
P341	If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P342	If experiencing respiratory symptoms:
P350	Gently wash with plenty of soap and water.
P351	Rinse cautiously with water for several minutes.
P352	Wash with plenty of soap and water.
P353	Rinse skin with water/shower.
P360	Rinse immediately contaminated clothing and skin with plenty of water before removing clothes.
P361	Remove/Take off immediately all contaminated clothing.
P362	Take off contaminated clothing and wash before reuse.
P363	Wash contaminated clothing before reuse.
P370	In case of fire:
P371	In case of major fire and large quantities:
P372	Explosion risk in case of fire.
P373	DO NOT fight fire when fire reaches explosives.
P374	Fight fire with normal precautions from a reasonable distance.
P376	Stop leak if safe to do so. Oxidising gases (section 2.4) 1
P377	Leaking gas fire: Do not extinguish, unless leak can be stopped safely.
P378
P380	Evacuate area.
P381	Eliminate all ignition sources if safe to do so.
P390	Absorb spillage to prevent material damage.
P391	Collect spillage. Hazardous to the aquatic environment
P301 + P310	IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.
P301 + P312	IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.
P301 + P330 + P331	IF SWALLOWED: Rinse mouth. Do NOT induce vomiting.
P302 + P334	IF ON SKIN: Immerse in cool water/wrap in wet bandages.
P302 + P350	IF ON SKIN: Gently wash with plenty of soap and water.
P303 + P361 + P353	IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.
P304 + P312	IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell.
P304 + P340	IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.
P304 + P341	IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P305 + P351 + P338	IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
P306 + P360	IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes.
P307 + P311	IF exposed: call a POISON CENTER or doctor/physician.
P308 + P313	IF exposed or concerned: Get medical advice/attention.
P309 + P311	IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician.
P332 + P313	IF SKIN irritation occurs: Get medical advice/attention.
P333 + P313	IF SKIN irritation or rash occurs: Get medical advice/attention.
P335 + P334	Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages.
P337 + P313	IF eye irritation persists: Get medical advice/attention.
P342 + P311	IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician.
P370 + P376	In case of fire: Stop leak if safe to Do so.
P370 + P378	In case of fire:
P370 + P380	In case of fire: Evacuate area.
P370 + P380 + P375	In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion.
P371 + P380 + P375	In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion.
Storage
Code	Phrase
P401
P402	Store in a dry place.
P403	Store in a well-ventilated place.
P404	Store in a closed container.
P405	Store locked up.
P406	Store in corrosive resistant/ container with a resistant inner liner.
P407	Maintain air gap between stacks/pallets.
P410	Protect from sunlight.
P411
P412	Do not expose to temperatures exceeding 50 oC/ 122 oF.
P413
P420	Store away from other materials.
P422
P402 + P404	Store in a dry place. Store in a closed container.
P403 + P233	Store in a well-ventilated place. Keep container tightly closed.
P403 + P235	Store in a well-ventilated place. Keep cool.
P410 + P403	Protect from sunlight. Store in a well-ventilated place.
P410 + P412	Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF.
P411 + P235	Keep cool.
Disposal
Code	Phrase
P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling

Physical hazards
Code	Phrase
H200	Unstable explosive
H201	Explosive; mass explosion hazard
H202	Explosive; severe projection hazard
H203	Explosive; fire, blast or projection hazard
H204	Fire or projection hazard
H205	May mass explode in fire
H220	Extremely flammable gas
H221	Flammable gas
H222	Extremely flammable aerosol
H223	Flammable aerosol
H224	Extremely flammable liquid and vapour
H225	Highly flammable liquid and vapour
H226	Flammable liquid and vapour
H227	Combustible liquid
H228	Flammable solid
H229	Pressurized container: may burst if heated
H230	May react explosively even in the absence of air
H231	May react explosively even in the absence of air at elevated pressure and/or temperature
H240	Heating may cause an explosion
H241	Heating may cause a fire or explosion
H242	Heating may cause a fire
H250	Catches fire spontaneously if exposed to air
H251	Self-heating; may catch fire
H252	Self-heating in large quantities; may catch fire
H260	In contact with water releases flammable gases which may ignite spontaneously
H261	In contact with water releases flammable gas
H270	May cause or intensify fire; oxidizer
H271	May cause fire or explosion; strong oxidizer
H272	May intensify fire; oxidizer
H280	Contains gas under pressure; may explode if heated
H281	Contains refrigerated gas; may cause cryogenic burns or injury
H290	May be corrosive to metals
Health hazards
Code	Phrase
H300	Fatal if swallowed
H301	Toxic if swallowed
H302	Harmful if swallowed
H303	May be harmful if swallowed
H304	May be fatal if swallowed and enters airways
H305	May be harmful if swallowed and enters airways
H310	Fatal in contact with skin
H311	Toxic in contact with skin
H312	Harmful in contact with skin
H313	May be harmful in contact with skin
H314	Causes severe skin burns and eye damage
H315	Causes skin irritation
H316	Causes mild skin irritation
H317	May cause an allergic skin reaction
H318	Causes serious eye damage
H319	Causes serious eye irritation
H320	Causes eye irritation
H330	Fatal if inhaled
H331	Toxic if inhaled
H332	Harmful if inhaled
H333	May be harmful if inhaled
H334	May cause allergy or asthma symptoms or breathing difficulties if inhaled
H335	May cause respiratory irritation
H336	May cause drowsiness or dizziness
H340	May cause genetic defects
H341	Suspected of causing genetic defects
H350	May cause cancer
H351	Suspected of causing cancer
H360	May damage fertility or the unborn child
H361	Suspected of damaging fertility or the unborn child
H361d	Suspected of damaging the unborn child
H362	May cause harm to breast-fed children
H370	Causes damage to organs
H371	May cause damage to organs
H372	Causes damage to organs through prolonged or repeated exposure
H373	May cause damage to organs through prolonged or repeated exposure
Environmental hazards
Code	Phrase
H400	Very toxic to aquatic life
H401	Toxic to aquatic life
H402	Harmful to aquatic life
H410	Very toxic to aquatic life with long-lasting effects
H411	Toxic to aquatic life with long-lasting effects
H412	Harmful to aquatic life with long-lasting effects
H413	May cause long-lasting harmful effects to aquatic life
H420	Harms public health and the environment by destroying ozone in the upper atmosphere

{[proInfo.proName]}

CAS No.: 412278-24-1

{[proInfo.proName]}