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[ CAS No. 67442-07-3 ] {[proInfo.proName]}

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Chemical Structure| 67442-07-3
Chemical Structure| 67442-07-3
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Product Details of [ 67442-07-3 ]

CAS No. :67442-07-3 MDL No. :MFCD00134232
Formula : C4H8ClNO2 Boiling Point : -
Linear Structure Formula :ClCH2CONCH3OCH3 InChI Key :SCOJKGRNQDKFRP-UHFFFAOYSA-N
M.W : 137.56 Pubchem ID :2734716
Synonyms :

Calculated chemistry of [ 67442-07-3 ]      Expand+

Physicochemical Properties

Num. heavy atoms : 8
Num. arom. heavy atoms : 0
Fraction Csp3 : 0.75
Num. rotatable bonds : 3
Num. H-bond acceptors : 2.0
Num. H-bond donors : 0.0
Molar Refractivity : 30.32
TPSA : 29.54 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : No
P-gp substrate : No
CYP1A2 inhibitor : No
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -6.86 cm/s

Lipophilicity

Log Po/w (iLOGP) : 1.32
Log Po/w (XLOGP3) : 0.39
Log Po/w (WLOGP) : 0.24
Log Po/w (MLOGP) : 0.42
Log Po/w (SILICOS-IT) : -0.13
Consensus Log Po/w : 0.45

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 2.0
Bioavailability Score : 0.55

Water Solubility

Log S (ESOL) : -0.74
Solubility : 25.0 mg/ml ; 0.182 mol/l
Class : Very soluble
Log S (Ali) : -0.58
Solubility : 36.5 mg/ml ; 0.265 mol/l
Class : Very soluble
Log S (SILICOS-IT) : -0.67
Solubility : 29.3 mg/ml ; 0.213 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 2.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 2.0

Safety of [ 67442-07-3 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P280 UN#:N/A
Hazard Statements:H302-H312-H332 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 67442-07-3 ]

* 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.

  • Upstream synthesis route of [ 67442-07-3 ]
  • Downstream synthetic route of [ 67442-07-3 ]

[ 67442-07-3 ] Synthesis Path-Upstream   1~8

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YieldReaction ConditionsOperation in experiment
92% With potassium carbonate In tert-butyl methyl ether; water at -5 - 20℃; for 3.5 h; Example 139
N-methoxy-N-methylchloroacetamide
A solution of N,O-dimethylhydroxylamine hydrochloride (200 g, 2.05 mol) and tert-butyl methyl ether (2 L) was added to a cooled (0°C) solution of potassium carbonate (624 g, 4.1 mol) in water (2 L).
The mixture was cooled to -5°C and chloroacetyl chloride added such that the temperature remained below 5°C.
The vigorously stirred mixture was allowed to warm to room temperature and stirred for an additional 3.5 hours.
The phases were separated and the aqueous phase was extracted with tert-butyl methyl ether (3 x 1 L).
The combined organic phase was washed with saturated aqueous sodium chloride solution (2 x 1 L), dried (MgSO4), and concentrated.
The residue was dried in vacuo to yield a white solid (257 g, 92percent).
Mp 39-40.5°C; 1H NMR (CDCl3, 300 MHz) δ 4.24 (s, 2 H), 3.74 (s, 3 H), 3.22 (s, 3 H); MS (CI) 138 (MH+); Anal. calcd for C4H8ClNO2: C, 34.92; H, 5.86; N, 10.18. Found: C, 35.06; H, 5.88; N, 10.23.
92% With potassium carbonate In tert-butyl methyl ether; water EXAMPLE 139 STR92 N-methoxy-N-methylchloroacetamide
A solution of N,O-dimethylhydroxylamine hydrochloride (200 g, 2.05 mol) and tert-butyl methyl ether (2 L) was added to a cooled (0° C.) solution of potassium carbonate (624 g, 4.1 mol) in water (2 L).
The mixture was cooled to -5° C. and chloroacetyl chloride added such that the temperature remained below 5° C.
The vigorously stirred mixture was allowed to warm to room temperature and stirred for an additional 3.5 hours.
The phases were separated and the aqueous phase was extracted with tert-butyl methyl ether (3*1 L).
The combined organic phase was washed with saturated aqueous sodium chloride solution (2*1 L), dried (MgSO4), and concentrated.
The residue was dried in vacuo to yield a white solid (257 g, 92percent).
Mp 39-40.5° C.; 1 H NMR (CDCl3, 300 MHz) δ 4.24 (s, 2 H), 3.74 (s, 3 H), 3.22 (s, 3 H); MS (CI) 138 (MH+); Anal. calcd for C4 H8 ClNO2: C, 34.92; H, 5.86; N, 10.18. Found: C, 35.06; H, 5.88; N, 10.23.
90% With potassium carbonate In tert-butyl methyl ether; water at -5 - 0℃; for 2 h; A 3 L four necked flask equipped with Teflon-blade stirrer, reflux condenser and thermo-pocket was charged with N-methoxymethanamine hydrochloride (345g), water (1 .6 litre) and the resulting reaction mixture was cooled to 0 to -5 °C. Then potassium carbonate (1466 g) was added in lots to the above reaction mixture followed by the addition of methyl tert-butyl ether (1 .4 litre). The chloroacetyl chloride (400 g) was dissolved in tert-butyl methyl ether (0.2 litre) and added dropwise in to the above kept reaction mixture at - 5°C to 0°C and the reaction mixture was stirred for 2 h at 0°C. The reaction mixture was allowed to come to ambient temperature and two phases were separated. The organic layer was dried over sodium sulfate, filtered and evaporated to provide 2-chloro-N-methoxy-N-methyl-acetamide as white solid (440 g, 90percent yield and 98.0percent area purity by HPLC).
Reference: [1] Journal of the American Chemical Society, [2] Journal of the American Chemical Society, 2009, vol. 131, p. 1077 - 1091
[3] European Journal of Organic Chemistry, 2017, vol. 2017, # 27, p. 3917 - 3920
[4] RSC Advances, 2013, vol. 3, # 26, p. 10158 - 10162
[5] Patent: EP1054881, 2008, B1, . Location in patent: Page/Page column 57
[6] Patent: US6051586, 2000, A,
[7] Patent: WO2018/177970, 2018, A1, . Location in patent: Page/Page column 70; 73
[8] Journal of the American Chemical Society, 2010, vol. 132, # 49, p. 17511 - 17515
[9] Journal of the American Chemical Society, 1990, vol. 112, # 19, p. 7001 - 7031
[10] Tetrahedron Letters, 1989, vol. 30, # 29, p. 3779 - 3780
[11] Journal of the American Chemical Society, 2008, vol. 130, # 10, p. 2916 - 2917
[12] Journal of Molecular Structure, 2010, vol. 977, # 1-3, p. 106 - 116
[13] Journal of Organic Chemistry, 2014, vol. 79, # 18, p. 8917 - 8925
[14] Dalton Transactions, 2015, vol. 44, # 45, p. 19464 - 19468
[15] Patent: US2016/83391, 2016, A1, . Location in patent: Paragraph 0595
[16] Angewandte Chemie - International Edition, 2017, vol. 56, # 38, p. 11594 - 11598[17] Angew. Chem., 2017, vol. 129, # 38, p. 11752 - 11756,5
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  • [ 1117-97-1 ]
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YieldReaction ConditionsOperation in experiment
94%
Stage #1: at 0℃; for 0.166667 h;
Stage #2: With phosphorus trichloride In toluene at 20 - 60℃; for 0.5 h;
General procedure: A solution of NHMe(OMe) (0.360 g, 6.0 mmol) and benzoic acid (0.244 g, 2.0 mmol) was stirred in dry toluene (10 mL) at 0 °C for 10 min. A solution of PCl3 (0.137 g, 1.0 mmol) in dry toluene (2 mL) was then added dropwise to the mixture. The mixture was warmed to r.t. slowly and then stirred at 60 °C for 0.5 h. When the reaction was complete (TLC monitoring), the mixture was cooled to r.t. The mixture was then quenched with sat. NaHCO3 soln (20 mL) and extracted with EtOAc (3 × 10 mL). The combined organic layers were dried (anhyd MgSO4). The solvent was removed in vacuo.The product was purified by column chromatography (silica gel, petroleum ether–EtOAc, 3:2) to give pure 3a as a colorless oil; yield: 320 mg (97percent).
Reference: [1] Synthesis (Germany), 2014, vol. 46, # 3, p. 320 - 330
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YieldReaction ConditionsOperation in experiment
5.1 kg
Stage #1: With potassium carbonate In tert-butyl methyl ether; water at 15 - 20℃; for 0.5 h;
Stage #2: at 5 - 20℃;
To a solution of 21.2 kg potassium carbonate K2CO3 (153.7 mol, 3.0 eq) in 30 L H20 was added, Ν,Ο-dimethylhydroxylamine 9 (CAS Reg. No. 1117-97-1) (5.0 kg, 51.3 mol, 1.0 eq) at 15-20 °C. The reaction was stirred at rt for 30min and 30 L methyl tert-butyl ether (TBME) was added. After stirred for 30min, the mixture was cooled to 5°C, and 11.6 kg of 2-Chloroacetyl chloride 8 (CAS Reg. No. 79-04-9 (102.7 mol, 2.0 eq) were added slowly. The reaction was stirred at rt overnight. Organics were separated from aqueous, and aqueous was extracted with TBME (30 L). The combined organics were washed with H20 (50 L), brine (50 L) and dried over Na2S04. Filtered and concentrated under vacuum afforded 5.1 kg of 2-chloro-N-methoxy- N-methylacetamide 10 (CAS Reg. No. 67442-07-3) as a white solid.
Reference: [1] Tetrahedron Letters, 1995, vol. 36, # 35, p. 6209 - 6212
[2] Tetrahedron Letters, 1998, vol. 39, # 12, p. 1509 - 1512
[3] Chemical Communications, 2014, vol. 50, # 27, p. 3619 - 3622
[4] Patent: WO2014/140073, 2014, A1, . Location in patent: Page/Page column 10; 25
[5] Patent: WO2014/139882, 2014, A1, . Location in patent: Paragraph 00444-00445
[6] Angewandte Chemie - International Edition, 2015, vol. 54, # 21, p. 6236 - 6240[7] Angew. Chem., 2015, vol. 54, # 21, p. 6334 - 6338
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YieldReaction ConditionsOperation in experiment
95% With potassium carbonate In water EXAMPLE 7
Preparation of N-methoxy-N-methylchloroacetamide (3b).
To a cold (0°C), stirred solution of K2CO3 (62.4 g, 450 mmol) in H2O (250 mL) was added, successively, N,O-dimethylhydroxylamine hydrochloride (20 g, 205 mmol) and organic solvent (250 mL, toluene or MTBE).
The resulting two phase mixture was cooled to -5°C and chloroacetyl chloride (19.6 ml, 246 mmol) was added over 5 min (solution temperature maintained below 0°C).
The vigorously stirred mixture was allowed to warm to 15°C over 30 min, the layers were separated, and the aqueous layer was extracted with organic solvent (3x100 mL, toluene or MTBE).
The combined organic extracts were concentrated (MTBE used as solvent) to give the amide 3b (26.8 g, 95percent) as a white solid.
Alternatively, the combined organic extracts (toluene used as solvent) were concentrated to 250 mL to effect azeotropic drying (water content 100μg/mL) and the solution of 3b was used directly in reactions with organometallic reagents.
Reference: [1] Patent: EP851850, 2001, B1,
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Reference: [1] Patent: WO2008/21213, 2008, A1, . Location in patent: Page/Page column 148-149
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  • [ 1634-04-4 ]
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  • [ 584-08-7 ]
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Reference: [1] Patent: US5786515, 1998, A,
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Reference: [1] Chemistry - A European Journal, 2005, vol. 11, # 17, p. 4935 - 4952
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  • [ 136592-00-2 ]
Reference: [1] Organic Process Research and Development, 2010, vol. 14, # 6, p. 1326 - 1336
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