196929-78-9

Usage

Uses

Used in Pharmaceutical Industry:
(R)-(+)-2-Methyl-2-propanesulfinamide is used as a chiral ligand for the development of pharmaceutical compositions. Its chiral properties enable the creation of enantiomerically pure compounds, which are essential in the production of effective and safe medications.
Used in Chemical Synthesis:
(R)-(+)-2-Methyl-2-propanesulfinamide is used as a useful reagent for synthesizing chiral amines, which are crucial building blocks in the development of various pharmaceuticals and agrochemicals.
Used in the Preparation of Beta-chloro Sulfinamides:
In the chemical industry, (R)-(+)-2-Methyl-2-propanesulfinamide is used as a key component in the synthesis of beta-chloro sulfinamides, which are important intermediates in the production of chiral azridines.
Used in the Preparation of Organocatalyst:
(R)-(+)-2-Methyl-2-propanesulfinamide is also utilized in the preparation of organocatalysts for enantioselective reduction of imines, a critical process in the synthesis of optically active compounds.
Used in the Synthesis of P,N-Sulfinyl Imine Ligands:
Furthermore, (R)-(+)-2-Methyl-2-propanesulfinamide is converted into P,N-sulfinyl imine ligands through condensation with aldehydes and ketones. These ligands are then used in iridium-catalyzed asymmetric hydrogenation of olefins, a significant process in the production of enantiomerically pure compounds.

InChI:InChI=1/C6H17NS.H2O/c1-6(2,3)8(4,5)7;/h7H2,1-5H3;1H2

Synthetic route

(RS,S)-N-(3-hydroxy-1,3-diphenylpropylidene)-tert-butanesulfinamide (441788-45-0) → (S)-3-hydroxy-1,3-diphenyl-propan-1-one (42052-51-7, 69897-46-7, 72237-27-5, 93059-59-7) + (R)-2-methylpropane-2-sulfinamide (196929-78-9)

Conditions	Yield
With acetic acid In methanol at 40℃; for 20h;	A 99% B n/a

(RS,S)-N-(3-hydroxy-4-methyl-1-phenylpentylidene)-tert-butanesulfinamide (441788-43-8) → (3S)-3-hydroxy-4-methyl-1-phenylpentan-4-one + (R)-2-methylpropane-2-sulfinamide (196929-78-9)

Conditions	Yield
With acetic acid In methanol at 40℃; for 20h;	A 98% B n/a

(R)-4-chloro-2-((R)-1-(4-methylphenylsulfonamido)ethyl)phenyl 2-methylpropane-2-sulfinate → (R)-N-(1-(5-chloro-2-hydroxyphenyl)ethyl)-4-methylbenzenesulfonamide (1421840-44-9) + (R)-2-methylpropane-2-sulfinamide (196929-78-9)

Conditions	Yield
With lithium hexamethyldisilazane In tetrahydrofuran at -10℃; for 2.5h; Concentration; Temperature; Time; Inert atmosphere;	A 94% B 85%

(R)-3-deoxy-1,2:5,6-di-O-isopropylidene-α-D-glucofuranos-3-yl tert-butanesulfinate (159263-57-7) → (R)-2-methylpropane-2-sulfinamide (196929-78-9)

Conditions	Yield
Stage #1: (R)-3-deoxy-1,2:5,6-di-O-isopropylidene-α-D-glucofuranos-3-yl tert-butanesulfinate With lithium hexamethyldisilazane In tetrahydrofuran at 0℃; for 48h; Inert atmosphere; Stage #2: With silica gel In tetrahydrofuran; methanol for 0.25h; Inert atmosphere;	92%
With aluminum oxide; potassium fluoride; lithium hexamethyldisilazane 1.) THF, from -78 deg C to RT, overnight, 2.) THF, 0 deg C, 1 h; Yield given. Multistep reaction;

2-Methyl-propane-2-sulfinic acid (1R,2S)-1-(2,4,6-trimethyl-benzenesulfonylamino)-indan-2-yl ester (861821-86-5) → (R)-2-methylpropane-2-sulfinamide (196929-78-9)

Conditions	Yield
With ammonia; lithium; ferric nitrate In tetrahydrofuran at -78℃; for 0.5h;	90%

2-Methyl-propane-2-sulfinic acid (1R,2S)-1-(2,4,6-trimethyl-benzenesulfonylamino)-indan-2-yl ester (446021-65-4) → (R)-2-methylpropane-2-sulfinamide (196929-78-9)

Conditions	Yield
With lithium amide; ammonia In tetrahydrofuran at -78℃;	90%

(4S,5R)-3-((S)-2-Methyl-propane-2-sulfinyl)-4,5-diphenyl-oxazolidin-2-one (813459-77-7) → (R)-2-methylpropane-2-sulfinamide (196929-78-9)

Conditions	Yield
With ammonia; lithium; ferric nitrate at -78℃; for 0.5h;	89%

(R)-tert-butylsulfinyl hydrazide → (R)-2-methylpropane-2-sulfinamide (196929-78-9)

Conditions	Yield
With acetic acid; zinc In dichloromethane at 35 - 42℃; for 16h; Green chemistry;	83%
With acetic acid; zinc In dichloromethane at 35 - 42℃; for 16h;	83%
With acetic acid; zinc In dichloromethane at 35 - 42℃; for 16h;	83%

(RS)-N-benzyl-2-methylpropane-2-sulfinamide (212378-92-2) → (R)-2-methylpropane-2-sulfinamide (196929-78-9)

Conditions	Yield
With ammonia; lithium; ammonium chloride at -40℃; for 0.5h;	82%

(R)-DAG tert-butylsulfinate → (R)-2-methylpropane-2-sulfinamide (196929-78-9)

Conditions	Yield
With lithium hexamethyldisilazane In tetrahydrofuran at -78℃; for 48h; Inert atmosphere; optical yield given as %ee; enantioselective reaction;	80%

(R)-tert-butyl tert-butanethiosulfinate (67734-35-4) → (R)-2-methylpropane-2-sulfinamide (196929-78-9)

Conditions	Yield
With n-butyllithium; ammonia at -50 - 0℃; for 1h; Temperature; Concentration; Solvent;	79%
With lithium amide; ammonia at -78℃; for 0.25h;	77%
With Iron(III) nitrate nonahydrate; lithium amide; ammonia at -78℃;	48%
With lithium amide; ammonia In tetrahydrofuran at -78℃; Yield given;

(1S)-(6-methoxyquinolin-4-yl)(5-vinylquinuclidin-2-yl)methyl-(R)-2-tert-butylsulfinate → (R)-2-methylpropane-2-sulfinamide (196929-78-9)

Conditions	Yield
With ammonia; lithium; ferric nitrate In tetrahydrofuran at -78℃; for 0.75h; Inert atmosphere; optical yield given as %ee; enantioselective reaction;	79%

quinine + tert-butylmagnesium chloride (677-22-5) → (R)-2-methylpropane-2-sulfinamide (196929-78-9)

Conditions	Yield
Stage #1: quinine With thionyl chloride; triethylamine at -78 - -37℃; for 1h; Stage #2: tert-butylmagnesium chloride at -78 - 75℃; for 2h; Stage #3: With lithium hexamethyldisilazane	70%

2-fluoro-1-(2-fluorophenyl)ethan-1-one (1402412-84-3) → (R)-2-methyl-propane-2-sulfinic acid [2-fluoro-1-(2-fluoro-phenyl)-eth-(E)-ylidene]-amide (1415914-97-4) + (R)-2-methylpropane-2-sulfinamide (196929-78-9)

Conditions	Yield
	A 62% B n/a

di-tert-butyl disulfide (110-06-5) → (R)-2-methylpropane-2-sulfinamide (196929-78-9)

Conditions	Yield
Stage #1: di-tert-butyl disulfide With bis(acetylacetonate)oxovanadium; (1S,2R)-1-(3,5-di-tert-butyl-2-hydroxybenzylideneamino)-2,3-dihydro-1H-inden-2-ol; dihydrogen peroxide In acetone at 0℃; Stage #2: With ammonia; lithium; ferric nitrate In tetrahydrofuran at -78℃;	60%

2-propyl tert-butanesulfinate (102101-45-1) → (R)-2-methylpropane-2-sulfinamide (196929-78-9)

Conditions	Yield
With Iron(III) nitrate nonahydrate; ammonia; lithium In 2-methyltetrahydrofuran at -65 - -50℃; Inert atmosphere;	60%

2-Methyl-propane-2-sulfinic acid ((R)-3-[1,3]dioxan-2-yl-1-phenyl-propyl)-amide (860640-13-7) → 2-phenyl-3,4-dihydro-2H-pyrrole + (R)-2-methylpropane-2-sulfinamide (196929-78-9) + trimethyleneglycol (504-63-2)

Conditions	Yield
With trifluoroacetic acid-d1 In water-d2 for 0.25h;

2-Methyl-propane-2-sulfinic acid (1R,2S)-1-(2,4,6-trimethyl-benzenesulfonylamino)-indan-2-yl ester (861821-86-5) → N-((1R,2S)-2-Hydroxy-indan-1-yl)-2,4,6-trimethyl-benzenesulfonamide (175848-32-5) + (R)-2-methylpropane-2-sulfinamide (196929-78-9)

Conditions	Yield
With lithium amide; ammonia at -78℃;

ethyl tert-butanesulfinate (120424-96-6) → (R)-2-methylpropane-2-sulfinamide (196929-78-9)

Conditions	Yield
With ammonia; sodium; ferric nitrate In cyclopentyl methyl ether at -48 - 20℃; Inert atmosphere; optical yield given as %ee;	6.47 g

C21H29NO4S2 (1310105-98-6) → C17H21NO3S (620627-46-5) + (R)-2-methylpropane-2-sulfinamide (196929-78-9)

Conditions	Yield
With lithium amide; ammonia at -60 - 20℃; Inert atmosphere; optical yield given as %ee; enantioselective reaction;

phenyl 2-methylpropane-2-sulfinate → (R)-2-methylpropane-2-sulfinamide (196929-78-9) + phenol (108-95-2)

Conditions	Yield
With lithium hexamethyldisilazane In tetrahydrofuran at 0 - 20℃; for 1.5h; Inert atmosphere;

phenyl 2-methylpropane-2-sulfinate → (R)-2-methylpropane-2-sulfinamide (196929-78-9) + (S)-2-methylpropane-2-sulfinamide (343338-28-3) + phenol (108-95-2)

Conditions	Yield
With lithium hexamethyldisilazane In tetrahydrofuran at 0 - 20℃; for 1.5h; Inert atmosphere;	A n/a B n/a C n/a

4-chlorophenyl 2-methylpropane-2-sulfinate → 4-chloro-phenol (106-48-9) + (R)-2-methylpropane-2-sulfinamide (196929-78-9)

Conditions	Yield
With lithium hexamethyldisilazane In tetrahydrofuran at 0 - 20℃; for 1h; Inert atmosphere;

4-methoxyphenyl 2-methylpropane-2-sulfinate → 4-methoxy-phenol (150-76-5) + (R)-2-methylpropane-2-sulfinamide (196929-78-9)

Conditions	Yield
With lithium hexamethyldisilazane In tetrahydrofuran at 0 - 20℃; Inert atmosphere;

2,2,2-trifluoro-1-phenylethyl 2-methylpropane-2-sulfinate → 1-phenyl-2,2,2-trifluoromethylethanol (340-04-5, 340-05-6) + (R)-2-methylpropane-2-sulfinamide (196929-78-9)

Conditions	Yield
With lithium hexamethyldisilazane In tetrahydrofuran at 0 - 20℃; for 10h; Inert atmosphere;

1,1,1,3,3,3-hexafluoro-2-phenylpropan-2-yl 2-methylpropane-2-sulfinate → 1,1,1,3,3,3-hexafluoro-2-(p-tolyl)propan-2-ol (2010-61-9) + (R)-2-methylpropane-2-sulfinamide (196929-78-9)

Conditions	Yield
With lithium hexamethyldisilazane In tetrahydrofuran at 0 - 20℃; for 3h; Inert atmosphere;

tert-butyl tert-butanethiosulfinate (31562-40-0) → (R)-2-methylpropane-2-sulfinamide (196929-78-9)

Conditions	Yield
Stage #1: tert-butyl tert-butanethiosulfinate With Iron(III) nitrate nonahydrate; ammonia; lithium In tetrahydrofuran at -78 - 20℃; for 16.75h; Inert atmosphere; Stage #2: With water; chloroacetic acid In tetrahydrofuran at 20℃; for 12.3333h; Inert atmosphere; Cooling with ice;

(+)-(S)-n-Propyl t-butylsulphinate (102101-42-8) → (R)-2-methylpropane-2-sulfinamide (196929-78-9)

Conditions	Yield
With Iron(III) nitrate nonahydrate; ammonia; sodium In tert-butyl methyl ether at -75 - -55℃; Inert atmosphere;	14.5 g

propionaldehyde (123-38-6) + (R)-2-methylpropane-2-sulfinamide (196929-78-9) → (R)-(-)-N-(propylidene)-2-methylpropane-2-sulfinamide (221375-47-9)

Conditions	Yield
With titanium(IV) tetraethanolate In tetrahydrofuran at 20℃; for 3h; Condensation;	100%
With magnesium sulfate In dichloromethane	96%
With copper(II) sulfate In dichloromethane for 20h; Inert atmosphere;	54%
With titanium(IV) isopropylate In tetrahydrofuran at 50℃;

3-methyl-butan-2-one (563-80-4) + (R)-2-methylpropane-2-sulfinamide (196929-78-9) → (R)-N-(3-methylbutan-2-ylidene)-2-methylpropane-2-sulfinamide (866993-51-3)

Conditions	Yield
With titanium(IV) tetraethanolate In tetrahydrofuran at 75℃;	100%
With titanium(IV) tetraethanolate In tetrahydrofuran Reflux;	75%
With titanium(IV) tetraethanolate In tetrahydrofuran at 60 - 75℃; Condensation;

3-phenyl-propionaldehyde (104-53-0) + (R)-2-methylpropane-2-sulfinamide (196929-78-9) → (RS,E)-(-)-N-(3-phenylpropyl)idene-tert-butanesulfinamide (336105-29-4)

Conditions	Yield
With titanium(IV) tetraethanolate In dichloromethane at 20℃; for 1.5h;	100%
With titanium(IV) tetraethanolate In tetrahydrofuran; isopropyl alcohol for 5h;	91%
With pyridinium p-toluenesulfonate; magnesium sulfate In dichloromethane at 20℃; for 24h;	90%

butyraldehyde (123-72-8) + (R)-2-methylpropane-2-sulfinamide (196929-78-9) → (RS,E)-N-butylidene-2-methylpropane-2-sulfinamide (479480-49-4)

Conditions	Yield
With molecular sieve; copper(II) sulfate In dichloromethane at 20℃;	100%
With pyridinium p-toluenesulfonate; magnesium sulfate In dichloromethane at 20℃; for 24h;	87%
With pyridinium p-toluenesulfonate; magnesium sulfate In dichloromethane at 20℃; for 20h;	85%

4-(4-fluoro-6-formyl-phenyl)-piperazine-1-carboxylic acid tert-butyl ester (697305-53-6) + (R)-2-methylpropane-2-sulfinamide (196929-78-9) → 4-{4-fluoro-2-[((RS)-2-methyl-propane-2-sulfinylimino)-methyl]-phenyl}-piperazine-1-carboxylic acid tert-butyl ester (869478-21-7)

Conditions	Yield
With titanium(IV) tetraethanolate In tetrahydrofuran; ethanol at 20℃; for 7h;	100%

4-(2-chloro-6-formyl-phenyl)-piperazine-1-carboxylic acid tert-butyl ester (869478-15-9) + (R)-2-methylpropane-2-sulfinamide (196929-78-9) → 4-{2-chloro-6-[((RS)-2-methyl-propane-2-sulfinylimino)-methyl]-phenyl}-piperazine-1-carboxylic acid tert-butyl ester

Conditions	Yield
With titanium(IV) tetraethanolate In tetrahydrofuran; ethanol at 20℃; for 24h;	100%

N-(4-acetyl-2,5-difluorophenyl)methanesulfonamide (910487-21-7) + (R)-2-methylpropane-2-sulfinamide (196929-78-9) → N-[4-((1R)-1-{[(R)-tert-butylsulfinyl]amino}ethyl)-2,5-difluorophenyl]methanesulfonamide (910487-22-8)

Conditions	Yield
Stage #1: N-(4-acetyl-2,5-difluorophenyl)methanesulfonamide; (R)-2-methylpropane-2-sulfinamide With titanium(IV) tetraethanolate In tetrahydrofuran at 70℃; for 30h; Stage #2: With sodium tetrahydroborate In tetrahydrofuran at 0 - 20℃; for 18h; Stage #3: With methanol; water In tetrahydrofuran	100%

N-(4-acetyl-2,6-difluorophenyl)methanesulfonamide (956901-21-6) + (R)-2-methylpropane-2-sulfinamide (196929-78-9) → N-[4-[(1R)-1-[[(R)-(1,1-dimethylethyl)sulfinyl]amino]ethyl]-2,6-difluorophenyl]methanesulfonamide (956901-22-7)

Conditions	Yield
Stage #1: N-(4-acetyl-2,6-difluorophenyl)methanesulfonamide; (R)-2-methylpropane-2-sulfinamide With titanium(IV) tetraethanolate In tetrahydrofuran at 70℃; for 18h; Stage #2: With sodium tetrahydroborate In tetrahydrofuran at -20 - 20℃; for 16h; Stage #3: With methanol; water In tetrahydrofuran	100%
Stage #1: N-(4-acetyl-2,6-difluorophenyl)methanesulfonamide; (R)-2-methylpropane-2-sulfinamide With titanium(IV) tetraethanolate In tetrahydrofuran at 70℃; for 18h; Stage #2: With sodium tetrahydroborate In tetrahydrofuran at -20 - 20℃; for 16h;	100%

ethyl 5-formyl-4-methyl-3-(pent-4-enyloxy)-1H-pyrrole-2-carboxylate (1020414-47-4) + (R)-2-methylpropane-2-sulfinamide (196929-78-9) → (R)-ethyl 4-methyl-5-[(2-methylpropan-2-ylsulfinyl)iminomethyl]-3-pent-4-enyloxy-1H-pyrrole-2-carboxylate (1020414-52-1)

Conditions	Yield
With titanium(IV) tetraethanolate In dichloromethane at 35℃; for 48h;	100%

(R)-2-methylpropane-2-sulfinamide (196929-78-9) + Cyclopropanecarboxaldehyde (1489-69-6) → [N(E),R(S)]-N-(cyclopropylmethylene)-2-methyl-2-propanesulfinamide (736947-01-6)

Conditions	Yield
With titanium(IV) tetraethanolate In tetrahydrofuran at 20℃; for 17h;	100%
With copper(II) sulfate In dichloromethane at 20℃; Inert atmosphere;	100%
With titanium(IV) tetraethanolate In tetrahydrofuran at 75℃; for 2h;	90%

isobutyraldehyde (78-84-2) + (R)-2-methylpropane-2-sulfinamide (196929-78-9) → (R)-N-(tert-butanesulfinyl)-N-(2-methylpropyliden)amine (196929-86-9)

Conditions	Yield
With titanium(IV) tetraethanolate In tetrahydrofuran at 20℃; for 24h; Inert atmosphere;	100%
With titanium(IV) tetraethanolate In tetrahydrofuran at 23℃; for 12h; Inert atmosphere;	82%
With titanium(IV) tetraethanolate at 70℃; for 0.166667h; Neat (no solvent); Microwave irradiation; Inert atmosphere;	53%

4-bromo-benzaldehyde (1122-91-4) + (R)-2-methylpropane-2-sulfinamide (196929-78-9) → (R)-N-(4-bromobenzylidene)-2-methylpropane-2-sulfinamide

Conditions	Yield
With titanium(IV) isopropylate In tetrahydrofuran at 20℃; for 16.0833h;	100%
With p-toluenesulfonic acid on sillica gel; water In neat (no solvent) for 0.5h; Sonication; Green chemistry;	95%
With boron trifluoride diethyl etherate In dichloromethane at 20℃; for 16h; Inert atmosphere;

(3aS,6S,6aS)-2,2-dimethyl-6-vinyltetrahydrofuro[3,4-d][1,3]dioxol-4-ol + (R)-2-methylpropane-2-sulfinamide (196929-78-9) → (R)-N-((3aS,4R,6S,6aS)-2,2-dimethyl-6-vinyl-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl)-2-methylpropane-2-sulfinamide (1359756-29-8)

Conditions	Yield
With caesium carbonate In dichloromethane for 3h; Reflux; Inert atmosphere; stereospecific reaction;	100%

4-chloro-3-fluoro-2-formylpyridine (1260878-78-1) + (R)-2-methylpropane-2-sulfinamide (196929-78-9) → (S,E)-N-((4-chloro-3-fluoropyridin-2-yl)methylene)-2-methylpropane-2-sulfinamide (1422510-26-6)

Conditions	Yield
With caesium carbonate In dichloromethane at 20℃; for 1h;	100%

4-cyanobenzaldehyde (105-07-7) + (R)-2-methylpropane-2-sulfinamide (196929-78-9) → (R)-(-)-N-(4-cyanobenzylidene)-2-methylpropane-2-sulfinamide (935263-24-4)

Conditions	Yield
With caesium carbonate In dichloromethane for 1h; Reflux;	100%
With p-toluenesulfonic acid on sillica gel In neat (no solvent) for 0.5h; Sonication; Green chemistry;	95%
With tetrafluoroboric acid diethyl ether; magnesium sulfate In dichloromethane at 20℃; for 2h;	91%

5-bromopyridine-3-carbaldehyde (113118-81-3) + (R)-2-methylpropane-2-sulfinamide (196929-78-9) → (R)-N-[(1E)-(5-chloropyridin-3-yl)methylidene]-2-methylpropane-2-sulfinamide

Conditions	Yield
With caesium carbonate In dichloromethane at 20℃;	100%

1-(benzo[d][1,3]dioxol-6-yl)ethanone (3162-29-6) + (R)-2-methylpropane-2-sulfinamide (196929-78-9) → (R)-N-(1-(benzo[d][1,3]dioxol-5-yl)ethylidene)-2-methylpropane-2-sulfinamide

Conditions	Yield
With titanium(IV) tetraethanolate In tetrahydrofuran at 20℃; for 30h; Time; Reflux;	100%
With titanium(IV) tetraethanolate In tetrahydrofuran for 35.5h; Reflux;
With titanium (IV) ethoxide In tetrahydrofuran at 20℃; for 35.5h; Reflux;
With titanium(IV) tetraethanolate In tetrahydrofuran at 65℃; for 6h; Inert atmosphere;

6-chloro-7-fluoro-2-oxo-1,2-dihydroquinoline-3-carbaldehyde + (R)-2-methylpropane-2-sulfinamide (196929-78-9) → (R,E)-N-((6-chloro-7-fluoro-2-oxo-1,2-dihydroquinolin-3-yl)methylene)-2-methylpropane-2-sulfinamide

Conditions	Yield
With titanium(IV) isopropylate In tetrahydrofuran at 20℃; for 24h; Inert atmosphere;	100%

1-tert-butoxycarbonyl-3-formylindole (57476-50-3) + (R)-2-methylpropane-2-sulfinamide (196929-78-9) → (R,E)-tert-butyl 3-(((tert-butylsulfinyl)imino)methyl)-1H-indole-1-carboxylate

Conditions	Yield
With titanium(IV) tetraethanolate at 20℃; for 12h; Inert atmosphere;	100%
With titanium (IV) ethoxide In tetrahydrofuran at 20℃; for 12h;	89%

allyl-N-methyl-N-(3-oxopropyl)carbamate + (R)-2-methylpropane-2-sulfinamide (196929-78-9) → (E)-allyl (3-((tert-butylsulfinyl)imino)propyl)(methyl)carbamate

Conditions	Yield
With pyridinium p-toluenesulfonate; magnesium sulfate In dichloromethane at 20℃;	100%

3-phenyl-propenal (104-55-2) + (R)-2-methylpropane-2-sulfinamide (196929-78-9) → (RS,E,E)-(-)-N-(3-phenylpropenyl)idene-tert-butanesulfinamide (364364-07-8)

Conditions	Yield
With titanium(IV) tetraethanolate In tetrahydrofuran at 20℃; Inert atmosphere;	100%

isoquinoline-8-carboxaldehyde (787615-01-4) + (R)-2-methylpropane-2-sulfinamide (196929-78-9) → (R)-N-(isoquinolin-8-ylmethylene)-2-methylpropane-2-sulfinamide

Conditions	Yield
With titanium(IV) tetraethanolate In tetrahydrofuran at 20℃; for 4h;	100%

2-chloro-6-fluorobenzaldehyde (387-45-1) + (R)-2-methylpropane-2-sulfinamide (196929-78-9) → (R,E)-N-(2-chloro-6-fluorobenzylidene)-2-methylpropane-2-sulfinamide

Conditions	Yield
With caesium carbonate In dichloromethane at 20℃; for 17h;	100%

(S)-3-phenylcyclopentanone (64145-51-3, 86505-44-4, 141662-68-2, 86505-50-2) + (R)-2-methylpropane-2-sulfinamide (196929-78-9) → C15H21NOS

Conditions	Yield
With titanium(IV) tetraethanolate In tetrahydrofuran at 75℃;	100%

4-chloro-3-fluoro-2-formylpyridine (1260878-78-1) + (R)-2-methylpropane-2-sulfinamide (196929-78-9) → (±)-(E)-N-((4-chloro-3-fluoropyridin-2-yl)methylene)-2-methylpropane-2-sulfinamide

Conditions	Yield
With caesium carbonate In dichloromethane at 20℃; for 1h;	100%

(R)-2-methylpropane-2-sulfinamide (196929-78-9) + 3-(cyclopropylmethoxy)-4-(difluoromethoxy)-benzaldehyde (151103-09-2) → (R)-2-methyl-2-propanesulfinic acid 3-cyclopropylmethoxy-4-(difluoromethoxy)benzylideneamide (1367625-78-2)

Conditions	Yield
With titanium(IV) tetraethanolate In tetrahydrofuran at 20℃; for 12h;	99.8%

4-chlorobenzaldehyde (104-88-1) + (R)-2-methylpropane-2-sulfinamide (196929-78-9) → (R)-(-)-N-[(1E)-(4-chlorophenyl)methylene]-2-methyl-2-propanesulfinamide (336105-23-8)

Conditions	Yield
With pyridinium p-toluenesulfonate; magnesium sulfate In dichloromethane at 20℃;	99%
With titanium(IV) tetraethanolate In tetrahydrofuran at 20℃; Ellmann's method;	95%
With titanium(IV) tetraethanolate In tetrahydrofuran at 22℃;	90%
With titanium(IV) tetraethanolate In dichloromethane at 20℃;
With titanium(IV) tetraethanolate In tetrahydrofuran at 20℃;

1-naphthaldehyde (66-77-3) + (R)-2-methylpropane-2-sulfinamide (196929-78-9) → (R)-(-)-2-methyl-N-[(1E)-1-naphthalenylmethylene]-2-propanesulfinamide (451503-13-2)

Conditions	Yield
With pyridinium p-toluenesulfonate; magnesium sulfate In dichloromethane at 20℃;	99%

benzaldehyde (100-52-7) + (R)-2-methylpropane-2-sulfinamide (196929-78-9) → (R)-N-benzylidene-2-methylpropane-2-sulfinamide (196929-85-8)

Conditions	Yield
With titanium(IV) tetraethanolate at 70℃; for 0.166667h; Neat (no solvent); Microwave irradiation; Inert atmosphere;	99%
With copper(II) sulfate In dichloromethane at 20℃;	99%
With titanium(IV) tetraethanolate In tetrahydrofuran at 20℃; for 24h; Inert atmosphere;	99%

Upstream product

• 67734-35-4 (R)-tert-butyl tert-butanethiosulfinate 
• 212378-92-2 (R_S)-N-benzyl-2-methylpropane-2-sulfinamide 
• 159263-57-7 (R)-3-deoxy-1,2:5,6-di-O-isopropylidene-α-D-glucofuranos-3-yl tert-butanesulfinate 
• 861821-86-5 2-Methyl-propane-2-sulfinic acid (1R,2S)-1-(2,4,6-trimethyl-benzenesulfonylamino)-indan-2-yl ester 
• 110-06-5 di-tert-butyl disulfide 
• 441788-43-8 (R_S,S)-N-(3-hydroxy-4-methyl-1-phenylpentylidene)-tert-butanesulfinamide 
• 441788-45-0 (R_S,S)-N-(3-hydroxy-1,3-diphenylpropylidene)-tert-butanesulfinamide 
• 446021-65-4 2-Methyl-propane-2-sulfinic acid (1R,2S)-1-(2,4,6-trimethyl-benzenesulfonylamino)-indan-2-yl ester 
• 120424-96-6 ethyl tert-butanesulfinate 
• 677-22-5 tert-butylmagnesium chloride 
• 1310105-98-6 C₂₁H₂₉NO₄S₂ 
• 31562-40-0 tert-butyl tert-butanethiosulfinate 
• 102101-42-8 (-)-(S)-n-propyl t-butylsulphinate 
• 102101-45-1 2-propyl tert-butanesulfinate 

Downstream Products

• 186249-76-3 (R,E)-2-methyl-N-(phenylmethylene)-2-propanesulfinamide 
• 220263-61-6 (R_S)-2-methyl-N-(1-phenylpentylidene)propane-2-sulfinamide 
• 221375-48-0 (N(E),R)-2-methyl-N-(2-phenylethylidene)-2-propanesulfinamide 
• 244092-54-4 (R,E)-N-(4-methoxybenzylidene)-2-methylpropane-2-sulfinamide 
• 220263-59-2 (R_S)-2-methyl-N-(1-phenylethylidene)propane-2-sulfinamide 
• 243671-49-0 (R)-N-hydrocinnamoyl-2-methyl-2-propanesulfinamide 
• 261761-41-5 (R)-(-)-N-[(4-allyldimethylsilylphenyl)methylene]-tert-butanesulfinamide 
• 393536-17-9 (R)-N-[(1E)-2-(benzyloxy)ethylidene]-2-methylpropane-2-sulfinamide 
• 364364-07-8 (R_S,E,E)-(-)-N-(3-phenylpropenyl)idene-tert-butanesulfinamide 
• 364364-13-6 (R)-(-)-N-(2-hexyl-3-phenyl-allylidene)-2-methylpropanesulfinamide 
• 364364-08-9 (R,E)-2-methyl-N-((E)-2-methyl-3-phenylallylidene)propane-2-sulfinamide 
• 364364-12-5 (R)-(-)-N-(2-pentyl-3-phenyl-allylidene)-2-methylpropanesulfinamide 
• 393536-49-7 (R_S)-N-(2-(1-benzyloxy)propylidene-2-methylpropane)sulfinamide 
• 336105-23-8 (R)-(-)-N-[(1E)-(4-chlorophenyl)methylene]-2-methyl-2-propanesulfinamide 

Relevant academic research and scientific papers

Improved synthesis of tert-butanesulfinamide suitable for large-scale production

(Matrix presented) An improved synthesis of tert-butanesulfinamide that overcomes the scalability problems of the previous syntheses is described. The key step is the catalytic asymmetric oxidation of the inexpensive di-tert-butyl disulfide starting material. The new homogeneous reaction conditions utilize an inexpensive chiral ligand prepared in a single step from commercially available cis-1-amino-indan-2-ol. The reaction is performed at a 2.3 M concentration in the practical solvent acetone and can readily be run on a kilogram scale.

Catalytic asymmetric oxidation of tert-butyl disulfide. Synthesis of tert-butanesulfinamides, tert-butyl sulfoxides, and tert-butanesulfinimines

The first example of the catalytic asymmetric oxidation of tert-butyl disulfide (1) is described. The product, tert-butyl tert-butanethiosulfinate (2) is obtained with 91% enantiomeric excess in yields of ≤92% on scales as large as 1 mol. The application of H2O2 as stoichiometric oxidant in the presence of 0.25 mol% of VO(acac)2 and 0.26 mol% of a chiral Schiff base ligand, 6a, is both convenient and cost-effective. Thiosulfinate ester 2 is chemically and optically stable and serves as an excellent precursor to chiral tert-butanesulfinyl compounds by the stereospecific nucleophilic displacement of tert-butyl thiolate. Addition of LiNH2 in liquid ammonia and THF provides tert-butanesulfinamide (3; 91% yield). A single recrystallization provides enantiomerically pure 3 in 71-75% overall yield from disulfide 1. Enantiomerically pure thiosulfinate ester 2 also reacts readily and stereospecifically with Grignard reagents, organolithiums, lithium amides, and lithium imine salts to provide enantiomerically pure chiral sulfoxides, sulfinamides, and sulfinimines in good yield.

Method for preparing chiral tert-butyl sulfinamide

The invention belongs to the technical field of chemical synthesis, and provides a method for preparing (R)-tert-butyl sulfinamide. The method comprises the following steps: (1) preparing a Grignard compound by using halogenated tert-butane as an initial raw material through a Grignard reaction, introducing sulfur dioxide gas into the Grignard reaction solution, and reacting to obtain tert-butyl sulfinic acid; (2) converting tert-butyl sulfinic acid into tert-butyl sulfinyl chloride by adopting thionyl chloride; (3) converting tert-butyl sulfinyl chloride into tert-butyl sulfinate through an alcohol reagent and an alkaloid compound; and (4) converting tert-butyl sulfinate into chiral (R)-tert-butyl sulfinate amine in the presence of ferric nitrate, lithium metal or sodium metal. Accordingto the method, the defects of an existing process are overcome, foul tert-butyl mercaptan is not used, used halogenated tert-butane and the like are common and cheap materials, alkaloid compounds canbe recycled, and the method is more suitable for industrial production.

Method of synthesizing enantiomerically pure tert-butanesulfinamide

The invention discloses a method of synthesizing enantiomerically pure tert-butanesulfinamide. The method comprises the following steps of using tert-butyl disulfide and hydrogen peroxide for selective oxidation, then performing reaction on a product and an acylation reagent to obtain tert-butylsulfinyl chloride or tert-butylsulfinyl bromide, then performing reaction on the tert-butylsulfinyl chloride or the tert-butylsulfinyl bromide and hydrazine hydrate to obtain tert-butylsulfinyl hydrazine, then performing reaction on the tert-butylsulfinyl hydrazine and a DTTA resolving agent for resolution and dissociation, and performing zinc/acetic acid pyrolysis to obtain the enantiomerically pure tert-butanesulfinamide. The method provided by the invention is simple, convenient and stable in technological operation and high in yield, is environmentally friendly, is cheap and available in raw materials compared with the prior art, lowers the production cost of the existing enantiomerically pure tert-butanesulfinamide and is beneficial to industrialized mass production.

Method for preparing enantiomer pure methylpropane-2-sulfinamide

The invention discloses a method for preparing enantiomer pure methylpropane-2-sulfinamide. The method comprises the following steps: performing selective oxidation on tertiary butyl dithioether and hydrogen peroxide; adding an acylation reagent so as to obtain tertiary butyl sulfonyl chloride or tertiary butyl thionyl bromide; adding hydrazine hydrate so as to obtain tertiary butyl thionyl hydrazine; further performing resolving dissociation with a tartaric acid resolving agent; performing cracking with zinc acetate, thereby obtaining the enantiomer pure methylpropane-2-sulfinamide. The method is simple and stable in process operation, high in yield and good in environment protection, and compared with a conventional process, the method is low in raw material price, easy in raw material obtaining, capable of reducing the production cost of conventional enantiomer pure methylpropane-2-sulfinamide, and beneficial to industrial on-scale production.

Method for preparing pure enantio-methylpropane-2-sulfinamide

The invention discloses a method for preparing pure enantio-methylpropane-2-sulfinamide. The method comprises the following steps: carrying out selective oxidation on di-tert-butyl disulfide and hydrogen peroxide, reacting with an acylation reagent so as to obtain tert-butylsulfinyl chloride and tertiary butyl sulfonyl bromide, further reacting with hydrazine hydrate so as to obtain tertiary butylhydrazide, further carrying out resolution and separation with a DBTA resolving agent, and carrying out cracking with zinc acetate, thereby obtaining the pure enantio-methylpropane-2-sulfinamide. Themethod is simple, convenient and stable in process operation, high in yield and good in environment protection, and compared with a conventional process, the method is cheap and easy in raw materialobtaining, low in production cost of pure enantio-methylpropane-2-sulfinamide, and beneficial to industrial on-scale production.

Process for synthesizing chiral tert-butanesulfinyl amide

The invention discloses a process for synthesizing chiral tert-butanesulfinyl amide. The process includes carrying out reaction on tert-butyl mercaptan and iodine/hydrogen peroxide acetone to generate di-tert-butyl disulfide; oxidizing hydrogen peroxide under the catalytic effect of vanadium to generate chiral tert-butyl sulfenyl tert-butyl mercaptide; carrying out one-pot reaction on the chiral tert-butyl sulfenyl tert-butyl mercaptide and lithium reagents/liquid ammonia in the presence of alkyl chloride to obtain the tert-butanesulfinyl amide. Compared with existing processes, the process has the advantages that the smoothness of the process can be enhanced, the usage of the liquid ammonia can be reduced to a great extent, and the operational efficiency can be improved.

NEW PROCESSES AND INTERMEDIATES USEFUL IN SYNTHESIS OF NEP INHIBITORS

The invention relates to a novel process, novel process steps and novel intermediates useful in the synthesis of pharmaceutically active compounds, in particular neutral endopeptidase (NEP) inhibitors such as sacubitril, and prodrugs thereof.

DMAP-Catalysed Sulfinylation of Diacetone- D -Glucose: Improved Method for the Synthesis of Enantiopure tert-Butyl Sulfoxides and tert-Butanesulfinamides

An improved method for the tert-butanesulfinylation of diacetone glucose with tert-butanesulfinyl chloride is reported. The method is based on a beneficial effect of catalytic DMAP, which enhances both the rate of the reaction and the enantioselectivity of the process to give (R S)-diastereomer 2 R S with a 94 % de and in quantitative yield. (R S)-DAG sulfinate ester 2 R S is an excellent intermediate for the synthesis of enantiopure tert-butyl sulfoxides. Grignard agents and organolithium reagents can displace smoothly the diacetone glucose moiety to give synthetically relevant enantiopure sulfoxides, including highly functionalized derivatives, in high yields and with high enantioselectivities. (R S)-DAG sulfinate ester 2 R S is also an excellent N-sulfinylating agent; simple addition of LiHMDS (lithium hexamethyldisilazide) in THF gives (S S)-tert-butanesulfinamide, and N-tert-butanesulfinylimines are then formed in a two-step one-pot manner. N-Alkylated tert-butanesulfinamides are formed by the condensation of 2 R S with lithium amides.

HALOGEN-ALKYL-1,3 OXAZINES AS BACE1 AND/OR BACE2 INHIBITORS

The present invention provides compounds of formula (I) having BACE1 and/or BACE2 inhibitory activity, their manufacture, pharmaceutical compositions containing them and their use as therapeutically active substances. The active compounds of the present invention are useful in the therapeutic and/or prophylactic treatment of e.g. Alzheimer's disease and type 2 diabetes.