3647-69-6

Basic information

• Product Name: 4-(2-Chloroethyl)morpholine hydrochloride
• Synonyms: 4-(2-chloroethyl)-morpholinhydrochloride;4-(2-chloroethyl)morpholinium chloride;N-(2-Chloroethyl)morpholine HCl;2-ChloroethylmorpholineHcl98%;2-Chloroethylmorpholine Hcl 98%;N-(2-Chloroethyl)morpholineHCl,[2-(N-Morpholino)ethylchlorideHCL];MOC;2-(n-morpholino)ethyl chloride hydrochloride
• CAS NO: 3647-69-6
• Molecular Formula: C₆H₁₂ClNO*ClH
• Molecular Weight: 186.08
• EINECS: 222-881-2
• Product Categories: Aromatic Morpholines;Building Blocks;C4 to C10;Chemical Synthesis;Halogenated Heterocycles;Heterocyclic Building Blocks;Morpholines/Thiomorpholines;Heterocycles;Pyridines
• Mol File: 3647-69-6.mol
• Article Data: 5

Chemical Properties

• Melting Point: 180-185 °C (dec.)(lit.)
• Boiling Point: 202.8 °C at 760 mmHg
• Flash Point: 76.4 °C
• Appearance: White to beige/Hygroscopic Crystalline Powder
• Density: 1.088g/cm3
• Vapor Pressure: 0.288mmHg at 25°C
• Storage Temp.: Store below +30°C.
• Water Solubility: soluble
• Sensitive: Hygroscopic
• BRN: 3684083
• CAS DataBase Reference: 4-(2-Chloroethyl)morpholine hydrochloride(CAS DataBase Reference)
• NIST Chemistry Reference: 4-(2-Chloroethyl)morpholine hydrochloride(3647-69-6)
• EPA Substance Registry System: 4-(2-Chloroethyl)morpholine hydrochloride(3647-69-6)

Safety Data

• Hazard Codes: T
• Statements: 21-25-34-43-52/53
• Safety Statements: 26-36/37/39-45-61
• RIDADR: UN 2923 8/PG 3
• WGK Germany: 2
• RTECS: QE0260000
• TSCA: Yes
• HazardClass: 8
• PackingGroup: III
• Hazardous Substances Data: 3647-69-6(Hazardous Substances Data)

Usage

Chemical Properties

White to beige crystalline powder

Uses

Different sources of media describe the Uses of 3647-69-6 differently. You can refer to the following data:
1. 4-(2-Chloroethyl)morpholine hydrochloride (MOC) is used as intermediate for the synthesis of pharmaceuticals (e.g. floredil, morinamide, nimorazole and pholcodine). Product Data Sheet
2. 4-(2-Chloroethyl)morpholine is used in the preparation of potential DNA cross-linking antitumor agents as well as synthetic opiate analogues. 4-(2-Chloroethyl)morpholine may possess sickle-cell hemogl obin aggregation inhibiting-activity.
3. 4-(2-Chloroethyl)morpholine hydrochloride (MOC) is used as intermediate for the synthesis of pharmaceuticals (e.g. floredil, morinamide, nimorazole and pholcodine). It is also used as Agrochemical Intermediates, dyestuff Intermediates.

Safety Profile

Experimental reproductive effects. Mutation data reported. When heated to decomposition it emits very toxic fumes of Cland NOx.

InChI:InChI=1/C6H12ClNO/c7-1-2-8-3-5-9-6-4-8/h1-6H2/p+1

Synthetic route

5-hydroxymethyl-6-methylazepino[4,5-b]indole → 1,2,3,4,5,6-hexahydro-3-morpholinoethyl-5-hydroxymethyl-6-methylazepino[4,5-b]indole + 4-(2-chloroethyl)morpholine hydrochride (3647-69-6)

trans-4-Bromo-N-methyl-N-[4-(2-morpholin-4-yl-ethoxy)-cyclohexyl]-benzenesulfonamide → trans-4-Bromo-N-(4-hydroxy-cyclohexyl)-N-methyl-benzenesulfonamide + 4-(2-chloroethyl)morpholine hydrochride (3647-69-6)

trans-N-Methyl-N-[4-(2-morpholin-4-yl-ethoxy)-cyclohexyl]-4-trifluoromethyl-benzenesulfonamide → trans-N-(4-hydroxy-cyclohexyl)-N-methyl-4-trifluoro-methyl-benzenesulfonamide + 4-(2-chloroethyl)morpholine hydrochride (3647-69-6)

morpholine (110-91-8) + 2-chloro-ethanol (107-07-3) → 4-(2-chloroethyl)morpholine hydrochride (3647-69-6)

Conditions	Yield
With thionyl chloride; sodium hydroxide In toluene for 5h; Reflux;
Stage #1: morpholine; 2-chloro-ethanol In toluene for 2h; Reflux; Stage #2: With thionyl chloride In toluene at 20℃; for 6.33h; Cooling with ice;	7.9 g

2-(morpholin-4-yl)ethanol (622-40-2) → 4-(2-chloroethyl)morpholine hydrochride (3647-69-6)

Conditions	Yield
With thionyl chloride In chloroform Reflux; Cooling with ice;

4-(2-chloroethyl)morpholine hydrochride (3647-69-6) + (3R,4R)-4-[4-(3-Benzyloxy-propoxy)-phenyl]-3-(7-hydroxy-naphthalen-2-ylmethoxy)-piperidine-1-carboxylic acid tert-butyl ester → (3R,4R)-4-[4-(3-Benzyloxy-propoxy)-phenyl]-3-[7-(2-morpholin-4-yl-ethoxy)-naphthalen-2-ylmethoxy]-piperidine-1-carboxylic acid tert-butyl ester

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 60℃; for 18h;	100%

4-(2-chloroethyl)morpholine hydrochride (3647-69-6) + (3R,4R)-4-[4-(3-Benzyloxy-propoxy)-phenyl]-3-(6-hydroxy-naphthalen-2-ylmethoxy)-piperidine-1-carboxylic acid tert-butyl ester → (3R,4R)-4-[4-(3-Benzyloxy-propoxy)-phenyl]-3-[6-(2-morpholin-4-yl-ethoxy)-naphthalen-2-ylmethoxy]-piperidine-1-carboxylic acid tert-butyl ester

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 60℃; for 18h;	100%

methyl 3-hydroxy-2-methylbenzoate (55289-05-9) + 4-(2-chloroethyl)morpholine hydrochride (3647-69-6) → methyl 2-methyl-3-(2-morpholinoethoxy)benzoate (467252-57-9)

Conditions	Yield
With potassium carbonate In acetonitrile Heating;	100%

4-(2-chloroethyl)morpholine hydrochride (3647-69-6) + methyl 4-hydroxylbenzoate (99-76-3) → methyl 4-(2-morpholinoethoxy)benzoate (92501-87-6)

Conditions	Yield
With potassium carbonate In acetonitrile at 50℃;	100%
With caesium carbonate In acetonitrile at 80 - 85℃; for 4h; Inert atmosphere;	92%
With potassium carbonate In acetone Heating;

4-hydroxy-2-nitroanisole (15174-02-4) + 4-(2-chloroethyl)morpholine hydrochride (3647-69-6) → 4-[2-(4-methoxy-3-nitro-phenoxy)-ethyl]-morpholine (761440-70-4)

Conditions	Yield
With potassium carbonate; potassium iodide In DMF (N,N-dimethyl-formamide) at 80℃; for 4h;	100%

4-bromo-phenol (106-41-2) + 4-(2-chloroethyl)morpholine hydrochride (3647-69-6) → 1-bromo-4-(2-morpholinoethoxy)benzene (836-59-9)

Conditions	Yield
With potassium carbonate In acetonitrile at 80℃; Product distribution / selectivity;	100%
With potassium carbonate In acetonitrile at 80℃; Product distribution / selectivity; Williamson Synthesis;	100%
With potassium carbonate In N,N-dimethyl-formamide at 60 - 65℃; for 17.5h; Product distribution / selectivity;	89%

4-(2-chloroethyl)morpholine hydrochride (3647-69-6) + methyl 4-hydroxylbenzoate (99-76-3) → 4-(2-morpholin-4-yl-ethoxy)-benzoic acid (134599-45-4)

Conditions	Yield
Stage #1: methyl 4-hydroxylbenzoate With potassium carbonate In DMF (N,N-dimethyl-formamide) at 100℃; Stage #2: 4-(2-chloroethyl)morpholine hydrochride In DMF (N,N-dimethyl-formamide) at 100℃; for 2h;	100%

(R)-ethyl 5-(2-(3-fluoro-5-hydroxyphenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carboxylate (1260846-73-8) + 4-(2-chloroethyl)morpholine hydrochride (3647-69-6) → (R)-ethyl 5-(2-(3-fluoro-5-(2-morpholinoethoxy)phenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carboxylate (1260846-75-0)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 15h;	100%

ethyl 7-(5-((4-(4-(tert-butoxycarbonyl)piperazin-1-yl)-phenoxy)methyl)-1,3-dimethyl-1H-pyrazol-4-yl)-3-(3-(naphthalen-1-yloxy)propyl)-1H-indole-2-carboxylate + 4-(2-chloroethyl)morpholine hydrochride (3647-69-6) → ethyl 7-(5-((4-(4-(tert-butoxycarbonyl)piperazin-1-yl)-phenoxy)methyl)-1,3-dimethyl-1H-pyrazol-4-yl)-1-(2-morpholinoethyl)-3-(3-(naphthalen-1-yloxy)propyl)-1H-indole-2-carboxylate

Conditions	Yield
With tetra-(n-butyl)ammonium iodide In N,N-dimethyl-formamide at 80℃; for 70h;	100%

tert-butyl N-(3,4-dichloro-5-hydroxyphenyl)carbamate (1130156-65-8) + 4-(2-chloroethyl)morpholine hydrochride (3647-69-6) → tert-butyl N-{3,4-dichloro-5-[2-(morpholin-4-yl)ethoxy]phenyl}carbamate

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 60℃; for 18h;	100%

methyl 3-hydroxy-[1,1’-biphenyl]-4-carboxylate (117369-94-5) + 4-(2-chloroethyl)morpholine hydrochride (3647-69-6) → methyl 3-(2-morpholinoethoxy)-[1,1’-biphenyl]-4-carboxylate

Conditions	Yield
With caesium carbonate In N,N-dimethyl-formamide at 85℃; for 3h; Inert atmosphere;	100%
With caesium carbonate In N,N-dimethyl-formamide at 85℃; for 3h; Inert atmosphere;	100%
With caesium carbonate In N,N-dimethyl-formamide at 85℃; for 3h; Inert atmosphere;	100%

4-(2-chloroethyl)morpholine hydrochride (3647-69-6) + 4'-(trifluoromethyl)-[1,1'-biphenyl]-4-sulfonyl chloride → N-(2-methylbut-3-yn-2-yl)-N-(2-morpholinoethyl)-4'-(trifluoromethyl)biphenyl-4-sulfonamide (1009101-86-3)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 90℃; for 19h;	99%

4-bromo-3-methylphenol (14472-14-1) + 4-(2-chloroethyl)morpholine hydrochride (3647-69-6) → 4-[2-(4-bromo-3-methylphenoxy)ethyl]-morpholine (947410-54-0)

Conditions	Yield
With potassium carbonate In acetonitrile at 80℃; for 3h;	99%

2-methyl-7-methoxy indole (53512-46-2) + 4-(2-chloroethyl)morpholine hydrochride (3647-69-6) → 4-(2-(7-methoxy-2-methyl-1H-indol-1-yl)ethyl)morpholine

Conditions	Yield
Stage #1: 4-(2-chloroethyl)morpholine hydrochride With potassium hydroxide In dimethyl sulfoxide for 0.0833333h; Stage #2: 2-methyl-7-methoxy indole In dimethyl sulfoxide at 100℃; for 3.5h;	99%

tert-butyl 2-(4-(methylsulfonamido)-1,3-dioxoisoindolin-2-yl)acetate (1431566-19-6) + 4-(2-chloroethyl)morpholine hydrochride (3647-69-6) → tert-butyl 2-(4-(N-(2-morpholinoethyl)-methylsulfonamido)-1,3-dioxoisoindolin-2-yl)acetate (1431566-28-7)

Conditions	Yield
With potassium carbonate In acetonitrile at 75℃;	99%
With potassium carbonate In acetonitrile at 75℃;	99%

2,3-difluorophenol (6418-38-8) + 4-(2-chloroethyl)morpholine hydrochride (3647-69-6) → 4-(2-(2,3-difluorophenoxy)ethyl)morpholine

Conditions	Yield
With tetra-(n-butyl)ammonium iodide; caesium carbonate In acetonitrile at 65℃; for 4h;	99%

(R)-3-(3-(3,4-dimethoxyphenyl)-1-hydroxypropyl)phenol + 4-(2-chloroethyl)morpholine hydrochride (3647-69-6) → (R)-3-(3,4-dimethoxyphenyl)-1-(3-(2-morpholinoethoxy)phenyl)-propan-1-ol (1374119-33-1)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 90℃; for 3h;	99%

4-(2-chloroethyl)morpholine hydrochride (3647-69-6) + 3,5-dibromotriazole (7411-23-6) → 4-[2-(3,5-dibromo-1,2,4-triazol-1-yl)ethyl]morpholine

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 50℃; Inert atmosphere;	99%

methyl 3-fluoro-9-hydroxy-6,7-dihydro-5H-dibenzo[a,c][7]annulene-2-carboxylate + 4-(2-chloroethyl)morpholine hydrochride (3647-69-6) → methyl 2-(3-fluoro-9-(2-morpholinoethoxy)-6,7-dihydro-5H-dibenzo[a,c][7]annulen-2-yl)acetate

Conditions	Yield
With caesium carbonate In N,N-dimethyl-formamide at 90℃; for 15h;	98.9%

1-(4-Hydroxyphenyl)-2-phenylethanone (2491-32-9) + 4-(2-chloroethyl)morpholine hydrochride (3647-69-6) → 1-[4-(2-morpholinoethoxy)phenyl]-2-phenylethanone

Conditions	Yield
With potassium carbonate In acetone for 6h; Heating;	98%

methyl 3-hydroxy-4-nitrobenzoate (713-52-0) + 4-(2-chloroethyl)morpholine hydrochride (3647-69-6) → methyl 3-(2-morpholinoethoxy)-4-nitrobenzoate

Conditions	Yield
With sodium carbonate In N,N-dimethyl-formamide at 80℃;	96.6%

4-(2-chloroethyl)morpholine hydrochride (3647-69-6) + 2-chloro-4-(p-hydroxyphenyl)pyrimidine → 4-{2-[4-(2-chloro-pyrimidin-4-yl)-phenoxy]-ethyl}-morpholine (866000-10-4)

Conditions	Yield
With potassium carbonate; potassium iodide In acetone for 16h; Heating / reflux;	96%

4-(2-chloroethyl)morpholine hydrochride (3647-69-6) + vanillin (121-33-5) → 3-methoxy-4-(2-morpholin-4-yl-ethoxy)benzaldehyde (46995-89-5)

Conditions	Yield
Stage #1: vanillin With potassium carbonate In acetonitrile for 0.5h; Stage #2: 4-(2-chloroethyl)morpholine hydrochride In acetonitrile for 8h; Reflux;	96%
With potassium carbonate In butanone for 6h; Reflux;
With potassium carbonate In dimethyl sulfoxide

2-(4-nitrophenyl)imidazo[2,1-b][1,3]benzothiazol-7-ol (914224-34-3) + 4-(2-chloroethyl)morpholine hydrochride (3647-69-6) → 4-(2-((2-(4-nitrophenyl)benzo[d]imidazo[2,1-b]thiazol-7-yl)oxy)ethyl)morpholine (950769-60-5)

Conditions	Yield
With tetra-(n-butyl)ammonium iodide; potassium carbonate In N,N-dimethyl-formamide at 90 - 95℃; for 5h;	96%
With tetra-(n-butyl)ammonium iodide; potassium carbonate In N,N-dimethyl-formamide at 90 - 95℃; for 5h; Product distribution / selectivity; Industry scale;	96%
With tetra-(n-butyl)ammonium iodide; potassium carbonate In N,N-dimethyl-formamide at 90℃; for 5h; Product distribution / selectivity;	95%

8-chloro-1-hydroxy-10,11-dihydrodibenzo[a,d]cyclohepten-5-one (1221486-64-1) + 4-(2-chloroethyl)morpholine hydrochride (3647-69-6) → 8-chloro-1-(2-morpholin-4-yl-ethoxy)-10,11-dihydrodibenzo[a,d]cyclohepten-5-one (1221486-67-4)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 80℃;	96%

2-[3-(benzyloxy)phenyl]-1,1-bis(4-hydroxyphenyl)-1-butene (1416136-82-7) + 4-(2-chloroethyl)morpholine hydrochride (3647-69-6) → 2-[3-(benzyloxy)phenyl]-1,1-bis{4-[2-(morpholin-4-yl)ethoxy]phenyl}-1-butene (1416136-86-1)

Conditions	Yield
Stage #1: 2-[3-(benzyloxy)phenyl]-1,1-bis(4-hydroxyphenyl)-1-butene With sodium hydride In N,N-dimethyl-formamide at 0 - 20℃; for 0.25h; Inert atmosphere; Stage #2: 4-(2-chloroethyl)morpholine hydrochride With ammonium chloride In N,N-dimethyl-formamide at 50℃; for 6h; Inert atmosphere;	96%
Stage #1: 2-[3-(benzyloxy)phenyl]-1,1-bis(4-hydroxyphenyl)-1-butene With sodium hydride In N,N-dimethyl-formamide at 0 - 20℃; for 0.25h; Stage #2: 4-(2-chloroethyl)morpholine hydrochride In N,N-dimethyl-formamide at 50℃; for 6h;	96%

(S)-methyl 1-(3-fluoro-2-methylphenyl)-3-(1H-pyrazol-4-yl)cyclopentanecarboxylate + 4-(2-chloroethyl)morpholine hydrochride (3647-69-6) → (S)-methyl 1-(3-fluoro-2-methylphenyl)-3-(1-(2-morpholinoethyl)-1H-pyrazol-4-yl)cyclopentanecarboxylate

Conditions	Yield
With caesium carbonate; potassium iodide In acetonitrile at 65℃; for 18h; Inert atmosphere;	96%

KD-114 (955121-59-2) + 4-(2-chloroethyl)morpholine hydrochride (3647-69-6) → 1,3-dimethyl-9-(4-(2-morpholinoethoxy)phenylethyl)-6,7,8,9-tetrahydropyrimido[2,1-f]purine-2,4(1H,3H)-dione

Conditions	Yield
With potassium carbonate In butanone for 10h; Reflux;	96%

Indole-3-carboxaldehyde (487-89-8) + 4-(2-chloroethyl)morpholine hydrochride (3647-69-6) → 1-(2-morpholin-4-yl-ethyl)-1H-indole-3-carbaldehyde (151409-85-7)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 50℃; for 48h;	95.4%
With potassium carbonate In N,N-dimethyl-formamide at 55℃; for 60h;	90%
With sodium hydride In N,N-dimethyl-formamide at 20℃; for 36h; Reflux;	52%
Stage #1: Indole-3-carboxaldehyde With caesium carbonate In acetonitrile at 60℃; for 2h; Stage #2: 4-(2-chloroethyl)morpholine hydrochride In acetonitrile at 60℃; for 1h;	49%

trans-6-methoxy-1,1-dimethyl-2,3-diphenyl-2,3-dihydro-1H-inden-4-ol + 4-(2-chloroethyl)morpholine hydrochride (3647-69-6) → C30H35NO3

Conditions	Yield
In isopropyl alcohol at 53 - 55℃; for 3h;	95.3%

Upstream product

• 622-40-2 2-(morpholin-4-yl)ethanol 
• 110-91-8 morpholine 
• 107-07-3 2-chloro-ethanol 

Downstream Products

• 117878-08-7 4-[2-(1,1-dimethyl-4-phenyl-piperidinium-4-ylmethoxy)-ethyl]-4-methyl-morpholinium; diiodide 
• 509-67-1 pholcodine 
• 59716-79-9 4-[2-(4,5-diphenyl-oxazol-2-ylsulfanyl)-ethyl]-morpholine 
• 33048-46-3 5-methyl-2-(2-morpholin-4-yl-ethyl)-6-phenyl-2H-pyridazin-3-one 
• 92623-83-1 pravadoline 
• 81068-26-0 3-[2-(4-morpholinyl)ethoxy]benzaldehyde 
• 79089-65-9 4-(2-(benzyloxy)ethyl)morpholine 
• 325775-21-1 N-(2-(4-methoxyphenyltelluro)ethyl)morpholine 
• 2089-21-6 1-(4-(2-morpholinoethoxy)phenyl)propan-1-one 
• 918531-87-0 4-[2-(1H-pyrrolo[2,3-b]pyridin-1-yl)ethyl]morpholine 
• 700804-23-5 4-(2-(2-methoxy-4-nitrophenoxy)ethyl)morpholine 

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