Name: 162359-55-9|2-Amino-2-(4-octylphenethyl)propane-1,3-diol|98%
Brand: Ambeed
SKU: A484670
Price: 6.0 USD
Availability: InStock
Rating: 95 (30 reviews)

1
[ 162358-09-0 ]
[ 162359-55-9 ]

Yield	Reaction Conditions	Operation in experiment
70 g	With sodium hydroxide; In methanol; water; for 2h;Reflux;	Example 10a Preparation of Fingolimod In a round bottom flask, 55 g of sodium hydroxide and 850 ml water was charged at about 25 C. 100 gm of compound of Formula X, obtained as in Example 9 or Example 9a, in 1200 ml of methanol was added to the above mixture and the mixture was refluxed under heating for 120 min. The reaction mass was cooled, 1000 ml of water was added and stirred. The solid obtained was filtered and washed with water to get 70 g of compound of Formula I Purity of compound: Product >99.5% and Impurity compound of Formula XII: <0.1% by HPLC. XRD Table of Fingolimod Base.
	With lithium hydroxide; In methanol; for 2h;Reflux;	Example 12 Preparation of (2-amino-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol (Fingolimod base) [Formula 6] To 2-Acetamido-2-(4-octylphenethyl) propane-1,3-diyl diacetate (formula 5a) (4 g) in methanol (12 mL), LiOH solution (12 mL) is added and the contents are heated to reflux and maintained for about 2 hours. The reaction mass is cooled to about 40 C. and evaporated Methanol under reduced pressure. The product is extracted to ethyl acetate (2*10 mL). The organic layer is washed with water (about 8 mL) followed by saturated sodium chloride solution (about 4 mL), dried over sodium sulphate and concentrated under reduced pressure. The contents are cooled to about 0-2 C., and the solids are stirred for about 1 hour and filtered. The wet cake is washed with chilled ethyl acetate (about 2 mL). The crude material is recrystallized using ethyl acetate to obtain Fingolimod base (formula 6) with chromatographic purity of about 99.6%.

Reference： [1]Journal of Medicinal Chemistry,2000,vol. 43,p. 2946 - 2961
[2]Patent: US2015/18578,2015,A1 .Location in patent: Paragraph 0195
[3]Patent: US2016/9634,2016,A1 .Location in patent: Paragraph 0114

2
[ 374077-88-0 ]
[ 162359-55-9 ]

Yield	Reaction Conditions	Operation in experiment
93%	With hydrogenchloride; hydrogen;palladium 10% on activated carbon; In methanol; isopropyl alcohol; at 20 - 50℃; under 750.075 - 26252.6 Torr; for 2.66667h;	Autoclave vessel was loaded with 3-(hydroxymethyl)-3-nitro-l-(4-octylphenyl)butane- 1,4-diol (10 g, 28.2 mmol) dissolved in MeOH (100 ml) followed by the addition of palladium /C (10%>) (3.00 g, 2.82 mmol) and hydrogen chloride solution in 2-propanol (0.539 ml, 2.82 mmol). System was stirred under hydrogen pressure (less than 1 bar) at room temperature. After 90 minutes of stirring, the pressure of hydrogen was increased to 35 bar and internal temperature increased from 21C to 50C (600 rpm). After 70 reaction minutes was reaction mixture filtered over celite and MeOH evaporated (40C, 210-15 mbar) to dryness.Yield: 8.3 g (93%) of pale grey solid material.
93%	With hydrogenchloride; hydrogen;palladium 10% on activated carbon; In methanol; isopropyl alcohol; at 20 - 50℃; under 750.075 - 26252.6 Torr; for 2.66667h;	Autoclave vessel was loaded with 3-(hydroxymethyl)-3-nitro-l-(4-octylphenyl)butane- 1,4-diol (10 g, 28.2 mmol) dissolved in MeOH (100 ml) followed by the addition of palladium /C (10%) (3.00 g, 2.82 mmol) and hydrogen chloride solution in 2-propanol (0.539 ml, 2.82 mmol). System was stirred under hydrogen pressure (less than 1 bar) at room temperature.After 90 minutes of stirring, the pressure of hydrogen was increased to 35 bar and internal temperature increased from 21C to 50C (600 rpm). After 70 reaction minutes was reaction mixture filtered over celite and MeOH evaporated (40C, 210-15 mbar) to dryness.Yield: 8.3 g (93%) of pale grey solid material.
2 g	With palladium 10% on activated carbon; hydrogen; In methanol; at 25 - 30℃; under 3000.3 - 3750.38 Torr; for 5h;	Example 10 Preparation of 2-amino-2-(4-octylphenethyl)propane-1,3-diol (Fingolimod Freebase) 2-nitro-2-(4-octylphenethyl)propane-1,3-diol (3 g) and methanol (60 mL) are charged into a hydrogenation vessel at 25-30 C. and stirred. 10% Pd/C (0.6 g) is charged into the vessel, a hydrogen pressure of 4-5 Kg/cm2 applied and the reaction mixture is maintained under the same conditions for about 5 hours. The reaction mixture is filtered through a hyflow bed and washed with methanol (10 mL). The obtained filtrate is concentrated under reduced pressure at a temperature below 36 C. to obtain 8 mL of concentrated reaction mass. n-Hexane (50 mL) is added, the reaction mixture is cooled to 0-5 C. and maintained at the same temperature for about 1 hour. The solid obtained is filtered, washed with n-hexane (10 mL) and dried under vacuum at 36 C. to give the title compound. Yield: 2.0 g Purity by HPLC: 99.1%

With palladium 10% on activated carbon; ammonium formate; In methanol; at 20℃; for 5h;

The proportion of 1: 3: 0.9: 0.03 by weight of the fingolimod intermediate I,Solvent, ammonium formate and catalyst were added to the reaction kettle, the solvent was methanol, the catalyst was 10% Pd /C;reaction at 20 C and thin layer chromatography or high performance liquid chromatography to determine the completion of the reaction, the reaction 5h;after the completion of the reaction, discharge, the release of the material for post-processing, and then hydrochloric acid acidification, the finished product.

Reference： [1]Patent: WO2012/41405,2012,A1 .Location in patent: Page/Page column 16-17
[2]Patent: WO2012/41707,2012,A1 .Location in patent: Page/Page column 14-15
[3]Synlett,2001,p. 1411 - 1414
[4]Patent: US2014/235895,2014,A1 .Location in patent: Paragraph 0234
[5]Patent: CN103896784,2016,B .Location in patent: Paragraph 0032-0034

3
[ 501-53-1 ]
[ 162359-55-9 ]
[ 402616-41-5 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium hydrogencarbonate; In water; ethyl acetate;	Step A: 2-Benzyloxycarbonylamino-2-hydroxymethyl-4-(4-(octyl)phenyl)butanol A mixture of 3.07 g (10.0 mmol) of 2-amino-2-hydroxymethyl-4-(4-(octyl)phenyl)butanol and 3.00 g (30.0 mmol) of KHCO3 in 200 mL of EtOAc and 150 mL of H2O was treated with 1.50 mL (10.0 mmol) of benzyl chloroformate, then stirred at rt for 2 h. The organic layer of the reaction mixture was separated, dried over MgSO4 and concentrated to afford 5.29 g of the title compound: 1H NMR (500 Mhz) delta0.88 (t, J=6.5, 3H), 1.22-1.34 (12H), 1.55-1.60 (m, 2H), 1.87-1.91 (m, 2H), 2.53-2.59 (4H), 3.23 (br s, 2H), 3.67 (dd, J=6.5, 11.5, 1H), 3.90 (dd, J=6.5, 11.5, 1H), 5.08 (s, 2H), 5.30 (s, 1H), 7.05-7.09 (4H), 7.32-7.36 (5H); HPLC A 5.34 min.

Reference： [1]Bioorganic and Medicinal Chemistry,2004,vol. 12,p. 4803 - 4807
[2]Patent: US2002/91105,2002,A1

4
[ 501-53-1 ]
[ 162359-55-9 ]
[ 847672-61-1 ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 5373 - 5377

5
[ 78-39-7 ]
[ 162359-55-9 ]
[ 402616-28-8 ]

Reference： [1]European Journal of Medicinal Chemistry,2006,vol. 41,p. 569 - 576

6
[ 885605-36-7 ]
[ 162359-55-9 ]

Yield	Reaction Conditions	Operation in experiment
95%		Compound (26, X = 2H) was hydrogenated in the same manner, affording compound (27) as a white solid. A solution of compound (27) (30 mmol) in CH2C12 (60 ml), TFA (50 ml), and water (30 ml) was stirred at room temperature overnight. The reaction mixture was quenched with NaHC03 solution and extracted with ethyl acetate. The organic solution was washed with water, brine and dried over Na2S04, filtered, and concentrated under vacuum to give the Fingolimod free base (95%) as a white solid, mp 120-124 C. The free base was transformed to its hydrochloride salt according to example 4.
69%		General procedure: A solution of 13a-i, 15a-c or 18 (0.11 mmol) in 10 mL methanol and 0.2 mL aqueous HCl (6 M) was heated at 50 C for 3 h. The solvent was then evaporated to dryness to give crude compound, which was treated with aq NaOH solution (2.5 mol/L) until pH¼8-9, the mixture was extracted with ethyl acetate (3 20 mL), and the combined organic layers were dried over anhydrous Na2SO4 and evaporated to dryness. The residue was purified by crystallization (CH2Cl2:MeOH¼15:1) to give pure 5aei, 6aec and Fingolimod, respectively.

Reference： [1]Synthesis,2006,p. 753 - 755
[2]Patent: WO2012/56458,2012,A2 .Location in patent: Page/Page column 29
[3]Tetrahedron,2013,vol. 69,p. 2927 - 2932

7
[ 885605-35-6 ]
[ 162359-55-9 ]

Reference： [1]Synthesis,2006,p. 753 - 755

8
[ 133826-41-2 ]
[ 162359-55-9 ]

Reference： [1]Synthesis,2006,p. 753 - 755

9
[ 364631-74-3 ]
[ 162359-55-9 ]

Reference： [1]Synthesis,2006,p. 753 - 755

10
[ 162359-55-9 ]
[ 903894-66-6 ]

Reference： [1]European Journal of Medicinal Chemistry,2006,vol. 41,p. 569 - 576

11
[ 162359-55-9 ]
[ 903894-68-8 ]

Reference： [1]European Journal of Medicinal Chemistry,2006,vol. 41,p. 569 - 576

12
[ 162359-55-9 ]
[ 903894-71-3 ]

Reference： [1]European Journal of Medicinal Chemistry,2006,vol. 41,p. 569 - 576

13
[ 162359-55-9 ]
[ 903894-70-2 ]

Reference： [1]European Journal of Medicinal Chemistry,2006,vol. 41,p. 569 - 576

14
[ 162359-55-9 ]
Octanoic acid [1-hydroxymethyl-3-(4-octyl-phenyl)-1-((2S,3R,4S,5R,6R)-3,4,5-trihydroxy-6-hydroxymethyl-tetrahydro-pyran-2-yloxymethyl)-propyl]-amide [ No CAS ]

Reference： [1]European Journal of Medicinal Chemistry,2006,vol. 41,p. 569 - 576

15
[ 162359-55-9 ]
Hexadecanoic acid [1-hydroxymethyl-3-(4-octyl-phenyl)-1-((2S,3R,4S,5R,6R)-3,4,5-trihydroxy-6-hydroxymethyl-tetrahydro-pyran-2-yloxymethyl)-propyl]-amide [ No CAS ]

Reference： [1]European Journal of Medicinal Chemistry,2006,vol. 41,p. 569 - 576

16
[ 162359-55-9 ]
Hexadecanoic acid [1-hydroxymethyl-3-(4-octyl-phenyl)-1-((2S,3S,4S,5S,6R)-3,4,5-trihydroxy-6-hydroxymethyl-tetrahydro-pyran-2-yloxymethyl)-propyl]-amide [ No CAS ]

Reference： [1]European Journal of Medicinal Chemistry,2006,vol. 41,p. 569 - 576

17
[ 162359-55-9 ]
Octanoic acid [1-benzyloxymethyl-3-(4-octyl-phenyl)-1-((2R,3R,4S,5S,6R)-3,4,5-tris-benzyloxy-6-benzyloxymethyl-tetrahydro-pyran-2-yloxymethyl)-propyl]-amide [ No CAS ]

Reference： [1]European Journal of Medicinal Chemistry,2006,vol. 41,p. 569 - 576

18
[ 162359-55-9 ]
Octanoic acid [1-benzyloxymethyl-3-(4-octyl-phenyl)-1-((2S,3R,4S,5S,6R)-3,4,5-tris-benzyloxy-6-benzyloxymethyl-tetrahydro-pyran-2-yloxymethyl)-propyl]-amide [ No CAS ]

Reference： [1]European Journal of Medicinal Chemistry,2006,vol. 41,p. 569 - 576

19
[ 162359-55-9 ]
Hexadecanoic acid [1-benzyloxymethyl-3-(4-octyl-phenyl)-1-((2R,3S,4S,5R,6R)-3,4,5-tris-benzyloxy-6-benzyloxymethyl-tetrahydro-pyran-2-yloxymethyl)-propyl]-amide [ No CAS ]

Reference： [1]European Journal of Medicinal Chemistry,2006,vol. 41,p. 569 - 576

20
[ 162359-55-9 ]
Hexadecanoic acid [1-benzyloxymethyl-3-(4-octyl-phenyl)-1-((2S,3S,4S,5R,6R)-3,4,5-tris-benzyloxy-6-benzyloxymethyl-tetrahydro-pyran-2-yloxymethyl)-propyl]-amide [ No CAS ]

Reference： [1]European Journal of Medicinal Chemistry,2006,vol. 41,p. 569 - 576

21
[ 162359-55-9 ]
Hexadecanoic acid [1-benzyloxymethyl-3-(4-octyl-phenyl)-1-((2R,3R,4S,5S,6R)-3,4,5-tris-benzyloxy-6-benzyloxymethyl-tetrahydro-pyran-2-yloxymethyl)-propyl]-amide [ No CAS ]

Reference： [1]European Journal of Medicinal Chemistry,2006,vol. 41,p. 569 - 576

22
[ 162359-55-9 ]
Hexadecanoic acid [1-benzyloxymethyl-3-(4-octyl-phenyl)-1-((2S,3R,4S,5S,6R)-3,4,5-tris-benzyloxy-6-benzyloxymethyl-tetrahydro-pyran-2-yloxymethyl)-propyl]-amide [ No CAS ]

Reference： [1]European Journal of Medicinal Chemistry,2006,vol. 41,p. 569 - 576

23
[ 162359-55-9 ]
[ 402616-23-3 ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 5373 - 5377

24
[ 162359-55-9 ]
[ 402616-26-6 ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 5373 - 5377

25
[ 162359-55-9 ]
[ 863225-34-7 ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 5373 - 5377

26
[ 162359-55-9 ]
Phosphoric acid mono-{(S)-4-[2-(4-octyl-phenyl)-ethyl]-2-oxo-oxazolidin-4-ylmethyl} ester [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 5373 - 5377

27
[ 162359-55-9 ]
Phosphoric acid mono-{(R)-4-[2-(4-octyl-phenyl)-ethyl]-2-oxo-oxazolidin-4-ylmethyl} ester [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 5373 - 5377

28
[ 162359-55-9 ]
phosphoric acid mono[(R/S)-2-hydroxymethyl-4-(4-octylphenyl)-2-(1-oxo-1,3-dihydroisoindol-2-yl)butyl]ester [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 5373 - 5377

29
[ 162359-55-9 ]
[ 847672-62-2 ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 5373 - 5377

30
[ 162359-55-9 ]
[ 863225-35-8 ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 5373 - 5377

31
[ 162359-55-9 ]
[ 863225-37-0 ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 5373 - 5377

32
[ 162359-55-9 ]
phosphoric acid mono[(S)-2-hydroxymethyl-4-(4-octylphenyl)-2-(1-oxo-1,3-dihydroisoindol-2-yl)butyl]ester [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 5373 - 5377

33
[ 162359-55-9 ]
phosphoric acid mono[(R)-2-hydroxymethyl-4-(4-octylphenyl)-2-(1-oxo-1,3-dihydroisoindol-2-yl)butyl]ester [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 5373 - 5377

34
[ 162359-55-9 ]
[ 402615-91-2 ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 5373 - 5377

35
[ 162359-55-9 ]
[ 402616-43-7 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2004,vol. 12,p. 4803 - 4807

36
[ 162359-55-9 ]
[ 402616-45-9 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2004,vol. 12,p. 4803 - 4807

37
[ 162359-55-9 ]
(+/-)-1-dibenzyloxyphosphoryloxy-2-benzyloxycarbonylamino-2-benzyloxymethyl-4-(4-(octyl)phenyl)butane [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry,2004,vol. 12,p. 4803 - 4807

38
[ 104-88-1 ]
resin-bound p-methylphenylboronic acid [ No CAS ]
[ 162359-55-9 ]

Reference： [1]Synlett,2001,p. 1411 - 1414

39
[ 150529-78-5 ]
[ 162359-55-9 ]

Reference： [1]Synlett,2001,p. 1411 - 1414

40
[ 49763-66-8 ]
[ 162359-55-9 ]

Reference： [1]Synlett,2001,p. 1411 - 1414

41
1-(4-octyl-phenyl)-prop-2-en-1-ol [ No CAS ]
[ 162359-55-9 ]

Reference： [1]Synlett,2001,p. 1411 - 1414

42
[ 374077-79-9 ]
[ 162359-55-9 ]

Reference： [1]Synlett,2001,p. 1411 - 1414

43
1-((E)-3-Nitro-propenyl)-4-octyl-benzene [ No CAS ]
[ 162359-55-9 ]

Reference： [1]Synlett,2001,p. 1411 - 1414

44
[ 374077-87-9 ]
[ 162359-55-9 ]

Reference： [1]Synlett,2001,p. 1411 - 1414
[2]Patent: US2014/235895,2014,A1

45
[ 374077-82-4 ]
[ 162359-55-9 ]

Reference： [1]Synlett,2001,p. 1411 - 1414

46
[ 111-64-8 ]
[ 162359-55-9 ]

Reference： [1]Journal of Medicinal Chemistry,2000,vol. 43,p. 2946 - 2961
[2]Patent: WO2014/111949,2014,A1
[3]Patent: WO2014/111949,2014,A1
[4]Patent: WO2014/111949,2014,A1
[5]Patent: US2015/18578,2015,A1

47
[ 103-45-7 ]
[ 162359-55-9 ]

Reference： [1]Journal of Medicinal Chemistry,2000,vol. 43,p. 2946 - 2961
[2]Patent: US2015/18578,2015,A1

48
[ 162358-08-9 ]
[ 162359-55-9 ]

Yield	Reaction Conditions	Operation in experiment
		To 2-(acetylamino)-2-(2-(4-octylphenyl)ethyl)propanedioic acid diethyl ester (0.50 g) [Formula 4] in Ethanol (8.5 mL) and water (2.0 mL), CaCl2 (0.32 g) is added and the reaction mixture is stirred for about 10 minutes-15 minutes. The reaction mass is cooled to about 10 C.-15 C. using ice bath. NaBH4 (0.21 g) is added portion wise and the reaction mixture is stirred for about 4 hours-20 hours at about 10-15 C. The reaction completion is monitored by TLC. To the reaction mass, 6M HCl (1.5 mL) is added and the reaction mass is heated to reflux. The refluxing is maintained for about 2 hours. After the disappearance of the starting material, the reaction mixture is cooled to about 10±5 C. and the pH is adjusted to about 9.5±0.5 by using 25% Sodium Hydroxide solution. 5 volumes of water is added followed by stirring for about 1 hour. The solids are filtered and the filtrate is recrystallized in ethyl acetate to obtain Fingolimod free base.

Reference： [1]Journal of Medicinal Chemistry,2000,vol. 43,p. 2946 - 2961
[2]Patent: US2014/170067,2014,A1
[3]Patent: US2015/18578,2015,A1
[4]Journal of Medicinal Chemistry,2015,vol. 58,p. 3471 - 3484
[5]Patent: US2016/9634,2016,A1 .Location in patent: Paragraph 0110
[6]Patent: US2016/9634,2016,A1
[7]Patent: US2016/9634,2016,A1
[8]Patent: US2016/9634,2016,A1
[9]Patent: WO2013/26765,2013,A1

49
[ 162358-07-8 ]
[ 162359-55-9 ]

Reference： [1]Journal of Medicinal Chemistry,2000,vol. 43,p. 2946 - 2961
[2]Patent: US2015/18578,2015,A1
[3]Patent: US2016/9634,2016,A1
[4]Patent: US2016/9634,2016,A1
[5]Patent: US2016/9634,2016,A1
[6]Patent: US2016/9634,2016,A1

50
[ 162358-05-6 ]
[ 162359-55-9 ]

Reference： [1]Journal of Medicinal Chemistry,2000,vol. 43,p. 2946 - 2961
[2]Patent: US2015/18578,2015,A1

51
[ 162358-04-5 ]
[ 162359-55-9 ]

Reference： [1]Journal of Medicinal Chemistry,2000,vol. 43,p. 2946 - 2961
[2]Patent: US2015/18578,2015,A1

52
[ 162358-06-7 ]
[ 162359-55-9 ]

Reference： [1]Journal of Medicinal Chemistry,2000,vol. 43,p. 2946 - 2961

53
[ 162358-03-4 ]
[ 162359-55-9 ]

Reference： [1]Journal of Medicinal Chemistry,2000,vol. 43,p. 2946 - 2961
[2]Patent: US2015/18578,2015,A1

54
[ 249289-10-9 ]
[ 162359-55-9 ]

Yield	Reaction Conditions	Operation in experiment
82%	With sodium hydroxide; In methanol; for 5h;Reflux;	Protected aminodiol 71 (349 mg, 1.0 mmol) was dissolved in methanol (20 mL) and treated with 1 M sodium hydroxide solution (1.2 mL, 1.2 mmol, 1.2 eq.). The reaction mixture was heated to reflux for 5 h. After cooling to r.t. the mixture was diluted with 1 M sodium hydroxide solution (15 mL) and the aqueous phase was extracted with dichloromethane (5 x 20 mL). The combined organic layers were dried over Na2S04 and concentrated in vacuo. The product was crystallized from ethyl acetate to give a white solid. Yield: 252 mg (82%). 72 M.p.: 127 C (lit. 121 -124 C) 1H-NMR (300 MHz, CD3OD, CDCI3) delta [ppm]: 0.87 (m, 3 H, 19-CH3), 1 .22-1.37 (m, 10 H, 14-CH2 to I 8-CH2), 1 .57 (m, 2 H, 13-CH2), 1 .69 (m, 2 H, 4-CH2), 2.51 -2.65 (m, 4 H, 5-CH2, 12-CHz), 3.48 (d, 2JH,H = 10.9 Hz, 2 H, 1 -CH2, 3-CH2), 3.54 (d, 2JH,H = 1 1.0 Hz, 2 H, 1 -CH2, 3-CHz), 7.09 (m, 4 H, 7-CH, 8-CH, 10-CH, 1 1 -CH). 13C-NMR (75 MHz, CD3OD, CDCI3) delta [ppm]: 14.3 (q, C-19), 23.2 (t, C-18), 29.5, 29.9, 30.1 (t, C-13 to C-16), 32.2 (t, C-5), 32.5 (t, C-4), 36.1 (t, C-17), 37.0 (t, C-12), 56.4 (s, C-2), 66.2 (t, C-1 , C-3), 128.7, 129.0 (d, C-7, C-8, C-10, C-1 1 ), 140.1 , 140.9 (s, C-6, C-9). Exact mass (ESI+): C19H33NO2 + H+: calcd. 308.2584, found 308.2585; C19H33NO2 + Na+: calcd. 330.2404, found 330.2408; + Na+: calcd. 637.4915, found 637.4917. Ref.: Spectroscopic data agree with those given in S. Kim, H. Lee, M. Lee, T. Lee, Synthesis 2006, 5, 753-755.
82%	With sodium hydroxide; In methanol; for 5h;Reflux;	12.5 2-Amino-2-(4-octylphenethyl)propane-1,3-diol (FTY 720) (SSS 798) Protected aminodiol 71 (349 mg, 1.0 mmol) was dissolved in methanol (20 mL) and treated with 1 M sodium hydroxide solution (1.2 mL, 1.2 mmol, 1.2 eq.). The reaction mixture was heated to reflux for 5 h. After cooling to r.t. the mixture was diluted with 1 M sodium hydroxide solution (15 mL) and the aqueous phase was extracted with dichloromethane (5*20 mL). The combined organic layers were dried over Na2SO4 and concentrated in vacuo. The product was crystallized from ethyl acetate to give a white solid. Yield: 252 mg (82%). M.p.: 127 C. (lit. 121-124 C.) 1H-NMR (300 MHz, CD3OD, CDCl3) delta [ppm]: 0.87 (m, 3H, 19-CH3), 1.22-1.37 (m, 10H, 14-CH2 to 18-CH2), 1.57 (m, 2H, 13-CH2), 1.69 (m, 2H, 4-CH2), 2.51-2.65 (m, 4H, 5-CH2, 12-CH2), 3.48 (d, 2JH,H=10.9 Hz, 2H, 1-CH2, 3-CH2), 3.54 (d, 2JH,H=11.0 Hz, 2H, 1-CH2, 3-CH2), 7.09 (m, 4H, 7-CH, 8-CH, 10-CH, 11-CH). 13C-NMR (75 MHz, CD3OD, CDCl3) delta [ppm]: 14.3 (q, C-19), 23.2 (t, C-18), 29.5, 29.9, 30.1 (t, C-13 to C-16), 32.2 (t, C-5), 32.5 (t, C-4), 36.1 (t, C-17), 37.0 (t, C-12), 56.4 (s, C-2), 66.2 (t, C-1, C-3), 128.7, 129.0 (d, C-7, C-8, C-10, C-11), 140.1, 140.9 (s, C-6, C-9). Exact mass (ESI+): C19H33NO2+H+: calcd. 308.2584, found 308.2585; C19H33NO2+Na+: calcd. 330.2404, found 330.2408; (C19H33NO2)2+Na+: calcd. 637.4915, found 637.4917. Ref.: Spectroscopic data agree with those given in S. Kim, H. Lee, M. Lee, T. Lee, Synthesis 2006, 5, 753-755.
73.94%	With lithium hydroxide; In methanol; at 25 - 30℃; for 2h;Reflux;	25-30C for 30 min. Reaction mass temperature was raised to reflux and maintained for 2 hours. Methanol was completely distilled under vacuum below 60C. Remaining mass was cooled to 25-30C. Compound was extracted with 300 ml of ethyl acetate. Organic layer was washed with. 100 ml of brine solution and dried with sodium sulphate. Sodium sulphate was filtered and ethyl acetate was completely distilled under vacuum at below 70C. Remaining crude mass was crystallized in 50 ml of hexane. Stirred the mass 30 min at 25-30C. Filtered the solid and washed with 20 ml of hexane. Compound was dried at 50-55C. Obtained solid weight: 6.50g. (Yield, 73.94 %). Purity by HPLC: 99.7% FT-IR (KBr) (Cm-1: 3351. 1, 2926.3, 2854.2, 1575.7, 1513.9, 1466.0, 1018.6, 965.6, 920.1 -1 HNMR (400 MHz, CDC13) delta- Value (ppm): 0.857-0:890 (t, 3H), 1.26-1.29(m, lOH), 1.57(m, 2H), 1.68-1.70(m, 2H), 1.90-2.30 (broad s, 4H), 2.535-2.62(m, 4H), 3.49- 3.525(d, 2H),3.59-3.62(d,2H), 7.10(s, 4H) 13 CNMR (400 MHz, DMSO-d6) delta- Value (ppm): 13.22(1C), 22.34(1C), 28.75 (lC), 28.91 (1C), 29.08(1 C), 31.34(1 C), 31.53(1C), 35.01(1C), 36.92 (1C), 55.52(2C), 65.33(2C), 128.39(4C), 139.57(1C), 140.67(1C). Mass: 309.51 [M+2], 308.5 [M+1]

21.5 g

With hydrogenchloride; water; In isopropyl alcohol;Reflux;

Example 6 Preparation of (2-amino-2[2-(4-octylphenyl)ethyl]propane-1,3-diol (Fingolimod base; Formula 6) N-[1,1-bis hydroxymethyl-3-(4-octylphenyl)propyl]acetamide (38 g) [Formula 5] in IPA (133 mL) and 6M HCl (133 mL) is taken and the contents are heated to reflux and the refluxing is maintained for about 2 hours. The reaction mass is cooled to about 40 C. and the IPA is evaporated under reduced pressure. Then, the pH of the reaction mass is adjusted to about 9-10 by using 25% NaOH solution and the product is extracted to ethyl acetate (3*114 mL). The organic layer is washed with water (114 mL) followed by saturated sodium chloride solution (2*38 mL), dried over sodium sulphate and concentrated under reduced pressure. The contents are cooled to about 0-2 C., the solids are stirred for about 1 hour and filtered. The wet cake is washed with chilled ethyl acetate (38 mL). The crude material is recrystallized using ethyl acetate to obtain Fingolimod base (Formula 6) in pure form (21.5 g).

Reference： [1]Patent: WO2013/26765,2013,A1 .Location in patent: Page/Page column 66-67
[2]Patent: US2014/170067,2014,A1 .Location in patent: Paragraph 0502; 0503; 0504; 0505; 0506; 0507
[3]Journal of Medicinal Chemistry,2015,vol. 58,p. 3471 - 3484
[4]Patent: WO2014/111949,2014,A1 .Location in patent: Page/Page column 30; 31
[5]Journal of Medicinal Chemistry,2000,vol. 43,p. 2946 - 2961
[6]Patent: US2016/9634,2016,A1 .Location in patent: Paragraph 0108
[7]Patent: US2016/9634,2016,A1
[8]Patent: US2016/9634,2016,A1

55
[ 162359-55-9 ]
[ 756-79-6 ]
1,1-Difluoro-3-amino-3-hydroxymethyl-5-(4-octylphenyl)pentylphosphonic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With n-butyllithium; In Diethyl difluoromethylphosphonate;	EXAMPLE 21 1,1-Difluoro-3-amino-3-hydroxymethyl-5-(4-octylphenyl)pentylphosphonic acid The title compound was prepared from 2-amino-2-hydroxymethyl-4-(4-(octyl)phenyl)butanol (FTY 720) using procedures analogous to those described in EXAMPLE 2, except that lithium diisopropylamide was substituted for n-butyllithium in Step C and diethyl difluoromethylphosphonate was substituted for dimethyl methylphosphonate in Step C: Mass spectrum (NH3-CI) 422 (M+H).

Reference： [1]Patent: US2002/91105,2002,A1

56
triethylorthoacetate [ No CAS ]
[ 162359-55-9 ]
[ 402616-28-8 ]

Yield	Reaction Conditions	Operation in experiment
440 mg (91%)	With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide;	Step A: (+/-)-2-Methyl-4-hydroxymethyl-4-(2-(4-octylphenyl)ethyl)oxazoline A solution of 450 mg (1.5 mmol) of 2-amino-2-hydroxymethyl-4-(4-(octyl)phenyl)butanol, 0.32 mL (1.75 mmol) of triethylorthoacetate and 0.56 mL (3.2 mmol) of DIEA in 6 mL of DMF was stirred at 75 C. for 2 h. The mixture was cooled, partitioned between 40 mL of 3:1 v/v ether/EtOAc and water and the layers were separated. The organic layer was washed with water and dried. Flash chromatography on silica gel using 4:1 v/v CH2Cl2/EtOAc as the eluant afforded 440 mg (91%) of the title compound: Mass spectrum (NH3-CI) 332 (M+H).

Reference： [1]Patent: US2002/91105,2002,A1

57
[ 162358-62-5 ]
[ 162359-55-9 ]

Yield	Reaction Conditions	Operation in experiment
	With lithium bromide; sodium borohydrid; In ethanol; water;	(3) 2-Amino-2-[2-(4-octylphenyl)ethyl]-1,3-propanediol A suspension of sodium borohydride (0.60 g) and lithium bromide (1.66 g) in ethanol (17 ml) was stirred at room temperature for 25 minutes. Ethyl 2-amino-2-ethoxycarbonyl-4(4-octylphenyl)butyrate (1.24 g) was dropwise added thereto over 3 minutes and the mixture was stirred at room temperature for 5 hours. Water (40 ml) was added to the reaction mixture and the mixture was stirred for 40 minutes. The crystals precipitated was collected by filtration and dried to give 0.68 g of the subject compound, melting point=125-126 C. Treatment of the subject compound with hydrochloric acid-ethanol gives the corresponding hydrochloride.

Reference： [1]Chemistry - A European Journal,2018,vol. 24,p. 9535 - 9541
[2]Patent: US5604229,1997,A

58
[ 141-82-2 ]
[ 162359-55-9 ]
2-amino-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol malonate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
92.3%	In isopropyl alcohol; at 82℃;Product distribution / selectivity;	FTY720 free base (1.63 mrnot) was dissolved in i-PrOH (6 ml) at 82 ºC.. Then a solution of malonic acid (0.815 mmol) in i-PrOH (1 ml) was added at 82 ºC.. Immediately after addition the product started to crystallize out. The suspension was cooled to room temperature. The product was collected by filtration and was washed with i-PrOH (2 ml). After drying at 50 C the product was obtained as white crystals in 92.3% yield.

Reference： [1]Patent: WO2010/55027,2010,A2 .Location in patent: Page/Page column 15

59
[ 64-19-7 ]
[ 162359-55-9 ]
[ 1227170-83-3 ]

Yield	Reaction Conditions	Operation in experiment
99.4%	In ethyl acetate; at 75℃;Product distribution / selectivity;	In an alternative procedure, FTY720 free base (2.27mmol) was dissolved in ethyl acetate (16ml) at 88-90 ºC.. Then a solution of acetic acid (2.5eq) in ethyl acetate (3ml) was added at 75ºC1. whereupon the product started to crystallize out immediately after addition. The resulting suspension was cooled to room temperature. The product was collected by filtration and was washed with ethyl acetate (2ml). After drying at 50 ºC. the product was obtained as white crystals in 99.4% yield.

Reference： [1]Patent: WO2010/55027,2010,A2 .Location in patent: Page/Page column 16

60
[ 802294-64-0 ]
[ 162359-55-9 ]
[ 1227170-84-4 ]

Yield	Reaction Conditions	Operation in experiment
96.9%	In ethyl acetate; at 70℃;Product distribution / selectivity;	In an alternative procedure. FTY720 free base (2.27mmol) was dissolved in ethyl acetate (16ml) at 88-90ºC. Then a solution of propionic acid (2.5eq) in ethyl acetate (3ml) was added at 70X1 whereupon the product started '.o crystallize out immediately after addition. The resulting suspension was cooled to room temperature. The product was collected by filtration and was washed with ethyl acetate (2ml). After drying at 50ºC the product was obtained as white crystals in 96.9% yield.

Reference： [1]Patent: WO2010/55027,2010,A2 .Location in patent: Page/Page column 17

62
[ 162359-55-9 ]
[ 1304017-22-8 ]
[ 1301696-39-8 ]

Yield	Reaction Conditions	Operation in experiment
	With iodine; silver trifluoromethanesulfonate; silver sulfate; In dichloromethane; at 20℃; for 18h;	Examples G and H: 2-Amino-2-[2-(3-iodo-4-octylphenyl)ethyl]-1 ,3-propandiol and 2- Amino-2-[2-(2-iodo-4-octylphenyl)ethyl]-1 ,3-propandiolTo a solution of FTY720 (3.2 g, 10.4 mmol) in 100 mL wet methylene chloride, silver sulphate (3.25 g, 10.4 mmol) and iodine (2.64 g, 10.41 mmol) are added. Silver trifluoromethanesulfonate (0.13 g, 0.52 mmol) is added at room temperature and the resulting mixture stirred for 18 hours at room temperature. The yellow solid silver iodide is filtered off. The organic phase is washed with 15% aqueous NaHC03, dried over sodium sulphate, filtered and evaporated to dryness.The residue is purified on a silica gel column to yield after drying a mixture of iodo compounds 7 and 8. Purification by chromatography (column: Chiralpak IC, 30x250 mm, mobile phase: C02/2-propanol/2-propylamine 75:25:0.25 (isocratic)) afforded the title compounds as white solid.Example G:LCMS RtB = 1.28 min, [M]+ = 433.9SFC Rtc = 4.82 min1H-NMR (500 MHz, DMSO-d6) delta ppm 7.62 (d, 1 H); 7.01 - 7.20 (m, 2 H); 4.43 (t, 2 H); 3.1 1 - 3.27 (m, 4 H); 2.55 - 2.63 (m, 2 H); 2.45 - 2.52 (m, 2 H); 1.38 - 1 .57 (m, 4 H); 1.16 - 1.35 (m, 12 H); 0.76 - 0.93 (m, 3 H)Example H:LCMS RtB = 1.29 min, [M]+ = 433.9SFC Rtc = 5.58 min1H-NMR (500 MHz, DMSO-d6) delta ppm 7.56 (d, 1 H); 7.06 - 7.21 (m, 2 H); 4.40 (t, 2 H); 3.17 - 3.27 (m, 4 H); 2.58-2.64 (m, 2 H); 2.41 - 2.47 (m, 2 H); 1.39-1 .42 (m, 2 H); 1.20-1 .31 (m, 12 H); 0.77 - 0.89 (m, 3 H)

Reference： [1]Patent: WO2011/70066,2011,A1 .Location in patent: Page/Page column 38
[2]ChemMedChem,2011,vol. 6,p. 667 - 677

63
[ 162359-55-9 ]
[ 1301696-45-6 ]

Reference： [1]Patent: WO2011/70066,2011,A1
[2]ChemMedChem,2011,vol. 6,p. 667 - 677

64
[ 162359-55-9 ]
[ 1311195-21-7 ]

Reference： [1]Patent: WO2011/70066,2011,A1

65
[ 162359-55-9 ]
[ 1301696-49-0 ]
phosphoric acid di-tert-butyl ester (R)-4-[2-(3-iodo-4-octylphenyl)ethyl]-2-oxooxazolidin-4-ylmethyl ester [ No CAS ]

Reference： [1]Patent: WO2011/70066,2011,A1
[2]ChemMedChem,2011,vol. 6,p. 667 - 677

66
[ 162359-55-9 ]
[ 1301696-56-9 ]

Reference： [1]Patent: WO2011/70066,2011,A1
[2]ChemMedChem,2011,vol. 6,p. 667 - 677

67
[ 162359-55-9 ]
[ 1311195-22-8 ]

Reference： [1]Patent: WO2011/70066,2011,A1

68
[ 162359-55-9 ]
[ 1301696-89-8 ]

Reference： [1]Patent: WO2011/70066,2011,A1

69
[ 162359-55-9 ]
C₃₂H₅₄BNO₆ [ No CAS ]

Reference： [1]Patent: WO2011/70066,2011,A1

70
[ 162359-55-9 ]
[ 1301696-92-3 ]

Reference： [1]Patent: WO2011/70066,2011,A1

71
[ 162359-55-9 ]
C₂₇H₄₄BF₃NO₄^(1-)*K⁽¹⁺⁾ [ No CAS ]

Reference： [1]Patent: WO2011/70066,2011,A1

72
[ 1339077-36-9 ]
[ 162359-55-9 ]

Reference： [1]Tetrahedron Letters,2011,vol. 52,p. 5672 - 5675

73
[ 1338833-97-8 ]
[ 162359-55-9 ]

Reference： [1]Tetrahedron Letters,2011,vol. 52,p. 5672 - 5675

74
fingolimod hydrochloride [ No CAS ]
[ 162359-55-9 ]

Yield	Reaction Conditions	Operation in experiment
	With ammonia; silica gel; In methanol; dichloromethane; water;	The free base of FTY720 was readily obtained by passing through silica gel in the presence of 1% aqueous ammonia (10:1 DCM:MeOH with 1% NH4OH) in accord with a literature protocol.5 1H NMR (600MHz, CD3OD): delta0.89 (3H, t, J = 7.0Hz, H-19), 1.22-1.35 (10H, m, H-14/15/16/17/18), 1.58 (2H, m, H-13), 1.66 (2H, m, H - 12), 2.55 (2H, t, J = 7.6Hz, H-12), 2.61 (2H, m, H-5), 3.46 (1H, d, J = 10.9Hz, H-2/3), 3.52 (1H, d, J = 10.9Hz, H-2/3), 7.06 (2H, d, J = 7.9Hz, H-8/10), 7.11 (2H, d, J = 7.9Hz, H-7/11). 13C NMR (150MHz, CD3OD): delta14.4, 23.7, 30.0, 30.3, 30.4, 30.6, 32.8, 33.0, 36.5, 37.6, 57.0, 66.5, 129.2, 129.4, 141.1, 141.3. Full NMR spectra are appended

Reference： [1]Tetrahedron Letters,2011,vol. 52,p. 5672 - 5675

76
[ 162359-55-9 ]
[ 1301696-41-2 ]

Reference： [1]ChemMedChem,2011,vol. 6,p. 667 - 677

77
[ 162359-55-9 ]
C₂₈H₄₇INO₅P [ No CAS ]

Reference： [1]ChemMedChem,2011,vol. 6,p. 667 - 677

78
[ 162359-55-9 ]
[ 1301696-48-9 ]
phosphoric acid di-tert-butyl ester (R)-4-[2-(2-iodo-4-octylphenyl)ethyl]-2-oxooxazolidin-4-ylmethyl ester [ No CAS ]

Reference： [1]ChemMedChem,2011,vol. 6,p. 667 - 677

79
[ 162359-55-9 ]
C₂₈H₄₇INO₅P [ No CAS ]

Reference： [1]ChemMedChem,2011,vol. 6,p. 667 - 677

80
[ 162359-55-9 ]
[ 1301696-52-5 ]

Reference： [1]ChemMedChem,2011,vol. 6,p. 667 - 677

81
[ 162359-55-9 ]
fingolimod hydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
96.5%	With hydrogenchloride; In ethanol; at 30 - 35℃; for 4h;	To a 500 ml four-necked flask connected with a stirrer, thermometer and reflux condenser, add 100 g of ethanol, 15.38 g (0.05 mol) of <strong>[162359-55-9]fingolimod</strong> (VI) obtained in the method of Example 6, 36.5 g (0.1 mol) 10 % Hydrogen chloride ethanol solution, stirred at 30-35 C for 4 hours, cooled to 20-25 C, filtered and dried to obtain 16.58 g of white solid <strong>[162359-55-9]fingolimod</strong> hydrochloride (), yield 96.5%, liquid purity 99.98 %.
93.88%	With hydrogenchloride; In methanol; at 25 - 55℃; for 0.5h;	ol) was dissolved in 60_ ml of methanol at 50-55C. Cooled to 25-30C._ 38.8 g of 2N hydrochloride solution was added and maintained for 30 min. 200 ml of ethyl acetate was added and stirred the mass for 15 min. Water , ethanol and ethyl acetate was completely distilled under vacuum below 70C. Remaining crude mass was dissolved in 30 ml methanol at 50-55C. 150 ml of ethyl acetate was added at 50-55C and stirred the mass for 15 min. Cooled to 25-30C and maintained for 1 hour. Solid was filtered and Washed with 25 ml of ethyl acetate. Compound was dried at 50-55C. Obtained' solid weight: 6.30g. (Yield, 93.88 %). FT-IR ( Br) (Cm-1'; 3371.9, 3266.6, 2922.3, 2851.4, 1601.8, 1069.6 1 HNMR (400 MHz, DMSO-d6) 6- Value (ppm): 0.833-0.867 (t,3H), L24-1.26(m, 10H), 1.528(m, 2H), 1.748-1.792(m,2H), 2.535-2.578(m, 4H), 3.512-3.525(d, 4H), 5.373- 5.398(t, 2H), 7.10(s, 4H), 7.84(s , 3H). 13 CNMR (400 MHz, DMSO-d6) delta- Value (ppm): 13.95(1C), 22.08(1C), 27.93(1C), 28.66 (1G), 28.82(1 C), 31.04(1C), 31.27(1C), 33.16(1C), 34.75(1C), 60.10(2C), 60.83(2C), 128.05(2C), 128.25(2C), 138.81(1C), 139.81 (1 C). Mass: 344.2 [M+1], 342.2 [M-1]
91%	With hydrogenchloride; In n-heptane; isopropyl alcohol; at 0 - 50℃; for 0.416667h;	<strong>[162359-55-9]Fingolimod</strong> (5 g, 16.1 mmol) was stirred with 2-propanol (30 ml). Into the heterogenic mixture, hydrogen chloride solution in 2-propanol (21%) (3.7 ml) was dropwise added. The heterogeneous mixture was warmed to 50C. Into resulting clear solution, pre-heated n-heptane (120 ml) was added slowly, while the homogeneity of the reaction mixture was maintained. Clear reaction mixture was stirred at a temperature of 50C for 10 min. The solution was cooled to 0C during 15 min. The resulted suspension was stirred at 0-3C for 40 min, filtered off, washed with 2 x 15 ml n-heptane. The yield of <strong>[162359-55-9]fingolimod</strong> hydrochloride was 5.1 g (91%) of off-white crystals.

88%	With hydrogenchloride; In hexane; isopropyl alcohol; at 60 - 65℃; for 1.08333h;	2-amino-2-(2-(4-octylphenyl)ethyl)propane-l ,3-diol (1 g, 3.24 mmol) was stirred with 2-propanoI (5 ml). Into heterogenic mixture, HC1 in 2-propanol (3.3 ml, 21 %) was dropwise added . The mixture was warmed to 65C. Solid material was completely dissolved. The solution was dropwise added into n-heptane (20 ml) for 5 min and intensively stirred.Formation of an off white precipitate was observed. Mixture was stirred for 60 min at 0C. The solid material was filtered off, washed with 2x5 ml of n-heptane and dried at 35C (10 mbar) for 120 min.Yield: 0.98 g (88%) of off white solid material with purity 99.97% (HPLC IN).
88%	With hydrogenchloride; In hexane; isopropyl alcohol; at 60 - 65℃; for 1.08333h;	2-amino-2-(2-(4-octylphenyl)ethyl)propane-l,3-diol (1 g, 3.24 mmol) was stirred with 2-propanol (5 ml). Into heterogenic mixture, anhydrous HC1 in 2-propanol (3.3 ml, 21 %) was dropwise added . The mixture was warmed to 65C. Solid material was completely dissolved. The solution was dropwise added into n-heptane (20 ml) for 5 min and intensively stirred. Formation of an off white precipitate was observed. Mixture was stirred for 60 min at 0C. The solid material was filtered off, washed with 2x5 ml of n-heptane and dried at 35C (10 mbar) for 120 min.Yield: 0.98 g (88%) of off white solid material with purity 99.97% (HPLC IN).
88%	With hydrogenchloride; In hexane; isopropyl alcohol; at 60 - 65℃; for 1.08333h;	2-amino-2-(2-(4-octylphenyl)ethyl)propane-l,3-diol (1 g, 3.24 mmol) was stirred with 2-propanol (5 ml). Into heterogenic mixture, anhydrous HCl in 2-propanol (3.3 ml, 21 %) was dropwise added. The mixture was warmed to 65C. Solid material was completely dissolved. The solution was dropwise added into n-heptane (20 ml) for 5 min and intensively stirred. Formation of an off white precipitate was observed. Mixture was stirred for 60 min at 0C. The solid material was filtered off, washed with 2x5 ml of n-heptane and dried at 35C (10 mbar) for 120 min.Yield: 0.98 g (88%) of off white solid material with purity 99.97% (HPLC IN).
85 g	With hydrogenchloride; In methanol; water; at 20℃; for 0.5h;	Example 11a Preparation of <strong>[162359-55-9]Fingolimod</strong> Hydrochloride 100.0 gm of <strong>[162359-55-9]fingolimod</strong> was dissolved in methanol 500 ml and conc HCl 49 ml solutions. The reaction mass was stirred for 30 min at room temperature and, then concentrated under vacuum at about 40-45 C. 250 ml of methanol was added. The reaction mass was heated to about 63-70 C. and 800 ml ethyl acetate was added in to reaction mass. The reaction mass was cooled to about 20-25 C. and stirred for about 30 min. The solid obtained was filtered and washed with ethyl acetate to get 85 g of compound of <strong>[162359-55-9]Fingolimod</strong> hydrochloride. Purity 99.75% Impurity compound of Formula XII: 0.06% by HPLC.PSD: particle size distribution D(10): 6 mum, D(50): 24.2 mum; D(90): 67.5 mum. Water content: 0.29% by Karl fischer. XRD Table of <strong>[162359-55-9]Fingolimod</strong> Hydrochloride
	With hydrogenchloride; In methanol; diethyl ether; at 20℃; for 1h;pH 4;	The discharged material was filtered, the mother liquor was concentrated to a white solid, and then a large amount of water was added. The mixture was stirred for another half hour and filtered to obtain a white solid.The white solid was dissolved in methanol. A solution of saturated hydrogen chloride in diethyl ether was added dropwise to rho H = 4 under ice-water bath. The mixture was stirred at room temperature for 1 h and the solvent was removed by concentration to obtain a white solid. The solid was recrystallized from ethanol / ethyl acetate to give the desired product. (99.96% purity by HPLC and less than 0.1% single impurity)
20 g	With hydrogenchloride; In ethyl acetate; isopropyl alcohol; at 70 - 80℃; for 1h;	Example 9 Preparation of <strong>[162359-55-9]Fingolimod</strong> Hydrochloride (Formula 1) [as provided by Scheme 1 of the present disclosure] <strong>[162359-55-9]Fingolimod</strong> base (21 g) [Formula 6] in ethyl acetate (63 mL), and HCl in IPA (15.75 mL) are charged together. The contents are stirred for about 1 hour at temperature of about 75+-5 C. The contents are then cooled to about 25-30 C. and the cooling is maintained for about 1 h at 25-30 C. The suspension is further cooled to about 0-5 C. and the said cooling is maintained for about 1 hour. The obtained solid after cooling is filtered and washed with chilled ethyl acetate (21 mL) and suck dried for about 1 hour under reduced pressure. The resultant is further dried for about 8-10 h at temperature of about 20-75 C. to get title compound (Formula 1) as white solid (20 g) with the chromatographic purity 99.7%.

Reference： [1]Patent: CN110938003,2020,A .Location in patent: Paragraph 0069-0102
[2]Patent: WO2014/111949,2014,A1 .Location in patent: Page/Page column 31; 32
[3]Patent: WO2012/89238,2012,A1 .Location in patent: Page/Page column 6
[4]Patent: WO2012/41359,2012,A1 .Location in patent: Page/Page column 14
[5]Patent: WO2012/41405,2012,A1 .Location in patent: Page/Page column 16
[6]Patent: WO2012/41707,2012,A1 .Location in patent: Page/Page column 14
[7]Patent: US2015/18578,2015,A1 .Location in patent: Paragraph 0198
[8]Patent: CN103896784,2016,B .Location in patent: Paragraph 0036; 0037
[9]Patent: US2016/9634,2016,A1 .Location in patent: Paragraph 0111

82
[ 899822-97-0 ]
[ 162359-55-9 ]

Reference： [1]Patent: WO2012/41359,2012,A1
[2]Patent: WO2012/41405,2012,A1
[3]Patent: WO2012/41707,2012,A1
[4]Patent: WO2012/41707,2012,A1
[5]Patent: US2014/235895,2014,A1
[6]Patent: US2014/235895,2014,A1

83
[ 899822-98-1 ]
[ 162359-55-9 ]

Reference： [1]Patent: WO2012/41359,2012,A1
[2]Patent: WO2012/41405,2012,A1
[3]Patent: WO2012/41707,2012,A1
[4]Patent: WO2012/41707,2012,A1
[5]Patent: US2014/235895,2014,A1

84
[ 899822-99-2 ]
[ 162359-55-9 ]

Yield	Reaction Conditions	Operation in experiment
76%		Autoclave vessel was loaded with p-toluenesulfonic acid monohydrate (8.04 g, 42.3 mmol), and with 3-(hydroxymethyl)-3-nitro-l-(4-octylphenyl)butane-l ,4-diol (5 g, 14.13 mmol) dissolved in MeOH (100 ml) followed by the addition of palladium /C (1.5 g, 1.410 mmol) . Autoclave was flushed twice with nitrogen and pressurized with hydrogen to 50 bar. The reaction mixture was hydrogenated at 50C and 600rpm.Total reaction time was 230 min.After this time, hydrogen pressure was interrupted and internal temperature decreased to 30C. Reaction mixture was filtered over celite and methanol was evaporated (50C, 200 mbar). Ethyl acetate (80 ml) was added to the white solid residue and the mixture was heated to 65C. Then 40 ml of aqueous solution of Na2C03 (0.5 mol) was added and ,at 50-55C, the biphasic mixture was allowed to settle after vigorous stirring .The organic phase was separated and the aqueous phase was extracted with 80 ml ethyl acetate under the same conditions twice more.. The combined organic layers were washed with 4x30 ml of water.Organic layer was dried with solid sodium sulphate at 55-60C and partially evaporated to a mass of 30 g (Formation of off white crystals observed during evaporation).The mixture was stored to freezer at -12C for 18 h. The solid material was filtered off, washed with 2x5 ml of ethyl acetate and dried at 30C, and 10 mbar for 120 min.Yield: 3.3 g (76%) of off white solid material with purity 99.8% (HPLC IN).
76%		Autoclave vessel was loaded with p-toluenesulfonic acid monohydrate (8.04 g, 42.3 mmol), and with 3-(hydroxymethyl)-3-nitro-l-(4-octylphenyl)butane-l,4-diol (5 g, 14.13 mmol) dissolved in MeOH (100 ml) followed by the addition of palladium /C (1.5 g, 1.410 mmol) . Autoclave was flushed twice with nitrogen and pressurized with hydrogen to 50 bar. The reaction mixture was hydrogenated at 50C and 600rpm.Total reaction time was 230 min.After this time, hydrogen pressure was interrupted and internal temperature decreased to 30C. Reaction mixture was filtered over celite and methanol was evaporated (50C, 200 mbar). Ethyl acetate (80 ml) was added to the white solid residue and the mixture was heated to 65C. Then 40 ml of aqueous solution of Na2C03 (0.5 mol) was added and ,at 50-55C, the biphasic mixture was allowed to settle after vigorous stirring .The organic phase was separated and the aqueous phase was extracted with 80 ml ethyl acetate under the same conditions twice more.. The combined organic layers were washed with 4x30 ml of water. Organic layer was dried with solid sodium sulphate at 55-60C and partially evaporated to a mass of 30 g (Formation of off white crystals observed during evaporation).The mixture was stored to freezer at -12C for 18 h. The solid material was filtered off, washed with 2x5 ml of ethyl acetate and dried at 30C, and 10 mbar for 120 min.Yield: 3.3 g (76%) of off white solid material with purity 99.8% (HPLC IN).
76%		Autoclave vessel was loaded with p-toluenesulfonic acid monohydrate (8.04 g, 42.3 mmol), and with 3-(hydroxymethyl)-3-nitro-l-(4-octylphenyl)butane-l,4-diol (5 g, 14.13 mmol) dissolved in MeOH (100 ml) followed by the addition of palladium/C (1.5 g, 1.410 mmol) . Autoclave was flushed twice with nitrogen and pressurized with hydrogen to 50 bar. The reaction mixture was hydrogenated at 50C and 600rpm. Total reaction time was 230 min. After this time, hydrogen pressure was interrupted and internal temperature decreased to 30C. Reaction mixture was filtered over celite and methanol was evaporated (50C, 200 mbar). Ethyl acetate (80 ml) was added to the white solid residue and the mixture was heated to 65C. Then 40 ml of aqueous solution of Na2C03 (0.5 mol) was added and ,at 50-55C, the biphasic mixture was allowed to settle after vigorous stirring .The organic phase was separated and the aqueous phase was extracted with 80 ml ethyl acetate under the same conditions twice more.. The combined organic layers were washed with 4x30 ml of water.Organic layer was dried with solid sodium sulphate at 55-60C and partially evaporated to a mass of 30 g (Formation of off white crystals observed during evaporation).The mixture was stored to freezer at -12C for 18 h. The solid material was filtered off, washed with 2x5 ml of ethyl acetate and dried at 30C, and 10 mbar for 120 min.Yield: 3.3 g (76%) of off white solid material with purity 99.8% (HPLC IN).

Reference： [1]Patent: WO2012/41359,2012,A1 .Location in patent: Page/Page column 13-14
[2]Patent: WO2012/41405,2012,A1 .Location in patent: Page/Page column 15-16
[3]Patent: WO2012/41707,2012,A1 .Location in patent: Page/Page column 13-14
[4]Patent: WO2012/41405,2012,A1

85
[ 899822-97-0 ]
(3-amino-5-(4-octylphenyl)tetrahydrofuran-3-yl)methanol [ No CAS ]
[ 162359-55-9 ]

Reference： [1]Patent: WO2012/41405,2012,A1
[2]Patent: WO2012/41707,2012,A1

86
[ 899822-98-1 ]
(3-amino-5-(4-octylphenyl)tetrahydrofuran-3-yl)methanol [ No CAS ]
[ 162359-55-9 ]

Reference： [1]Patent: WO2012/41405,2012,A1
[2]Patent: WO2012/41707,2012,A1

87
[ 899822-99-2 ]
(3-amino-5-(4-octylphenyl)tetrahydrofuran-3-yl)methanol [ No CAS ]
[ 162359-55-9 ]

Reference： [1]Patent: WO2012/41405,2012,A1

88
[ 1369968-69-3 ]
[ 162359-55-9 ]

Yield	Reaction Conditions	Operation in experiment
86%	With hydrogenchloride; hydrogen;palladium 10% on activated carbon; In methanol; isopropyl alcohol; at 100℃; under 26252.6 Torr; for 2h;	Autoclave vessel was loaded with (3-nitro-5-(4-octylphenyl)tetrahydrofuran-3-yl)- methanol (compound (11), 5 g, 14.91 mmol) dissolved in methanol (100 ml) followed addition of palladium/C (10%) (anhydrous) (1.586 g, 1.491 mmol) and hydrogen chloride solution in 2-propanol (11.23 ml, 59.6 mmol). The autoclave was flushed twice with nitrogen and pressurized with hydrogen up to 35 bars and heated to 100 C. The reaction mixture was stirred (600 rpm) at this temperature for 2 hours. After this time was internal temperature of reaction mixture decreased to 30C and filtered over celite. MeOH was evaporated (40C, 210-15 mbar) to dryness .Yield: 4.2 g (86%>) of grey solid material.
86%	With hydrogenchloride; hydrogen;palladium 10% on activated carbon; In methanol; isopropyl alcohol; at 100℃; under 26252.6 Torr; for 2h;	Autoclave vessel was loaded with (3-nitro-5-(4-octylphenyl)tetrahydrofuran-3-yl)- methanol (compound (11), 5 g, 14.91 mmol) dissolved in methanol (100 ml) followed addition of palladium/C (10%) (anhydrous) (1.586 g, 1.491 mmol) and hydrogen chloride solution in 2-propanol (11.23 ml, 59.6 mmol). The autoclave was flushed twice with nitrogen and pressurized with hydrogen up to 35 bars and heated to 100 C. The reaction mixture was stirred (600 rpm) at this temperature for 2 hours. After this time was internal temperature of reaction mixture decreased to 30C and filtered over celite. MeOH was evaporated (40C, 210-15 mbar) to dryness .Yield: 4.2 g (86%>) of grey solid material.

Reference： [1]Patent: WO2012/41405,2012,A1 .Location in patent: Page/Page column 17
[2]Patent: WO2012/41707,2012,A1 .Location in patent: Page/Page column 15

89
[ 1369968-69-3 ]
(3-amino-5-(4-octylphenyl)tetrahydrofuran-3-yl)methanol [ No CAS ]
[ 162359-55-9 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogen;5%-palladium/activated carbon; In toluene; at 30℃; under 26252.6 Torr; for 2h;	Autoclave vessel was loaded with (3-nitro-5-(4-octylphenyl)tetrahydrofuran-3- yl)methanol (2 g, 5.96 mmol) dissolved in toluene (60 ml) followed by the addition of palladium /C (5%>) (0.063 g, 0.596 mmol). Autoclave was flushed twice with nitrogen and pressurized with hydrogen up to 35 bar at 30C (600 rpm).After 120 reaction minutes was reaction mixture filtered over celite and solvent evaporated (50C, 90-15 mbar). Yield: 1.8 g (90%) of dark grey solid material which contains mixture of desired product (14) and fingolimod in mutual ratio 70 / 30 (measured by HPLC IN).
	With hydrogen;5%-palladium/activated carbon; In toluene; at 30℃; under 26252.6 Torr; for 2h;	Autoclave vessel was loaded with (3-nitro-5-(4-octylphenyl)tetrahydrofuran-3- yl)methanol (2 g, 5.96 mmol) dissolved in toluene (60 ml) followed by the addition of palladium /C (5%>) (0.063 g, 0.596 mmol). Autoclave was flushed twice with nitrogen and pressurized with hydrogen up to 35 bar at 30C (600 rpm).After 120 reaction minutes was reaction mixture filtered over celite and solvent evaporated (50C, 90-15 mbar). Yield: 1.8 g (90%) of dark grey solid material which contains mixture of desired product (14) and fingolimod in mutual ratio 70 / 30 (measured by HPLC IN).

Reference： [1]Patent: WO2012/41405,2012,A1 .Location in patent: Page/Page column 17-18
[2]Patent: WO2012/41707,2012,A1 .Location in patent: Page/Page column 15

90
[ 139512-81-5 ]
[ 162359-55-9 ]

Reference： [1]Patent: WO2012/56458,2012,A2
[2]Patent: WO2012/56458,2012,A2

91
[ 1373549-77-9 ]
[ 162359-55-9 ]

Reference： [1]Patent: WO2012/56458,2012,A2

92
[ 1373549-78-0 ]
[ 162359-55-9 ]

Reference： [1]Patent: WO2012/56458,2012,A2

93
[ 104-15-4 ]
[ 162359-55-9 ]
[ 1377321-92-0 ]

Yield	Reaction Conditions	Operation in experiment
	In ethanol; at 20 - 22℃; for 16h;	Example 1: Synthesis of <strong>[162359-55-9]Fingolimod</strong> Tosylate5.00 g of <strong>[162359-55-9]Fingolimod</strong> free base (16.3 mmol) were dissolved in 100 mL hot ethanol (absolute, >99%). 3.25 g p-toluenesulfonic acid (17.1 mmol) were added to the solution in five portions (each 0.65 g). The solution was left standing at ambient temperature (about 20C to about 22C) for 16h. After that, the reaction mixture was cooled to -18C and left standing for additional 24h at the same temperature, in order to complete crystallisation. The precipitated crystals were filtrated off at ambient temperature (about 20C to about 22C), washed with cool (about 4C to about 6C) ethanol (absolute, >99%) and dried at 50C for 24h (on normal atmospheric air). .Yield: 4.01 g (8.4 mmol)Melting point: 156.8CXRPD shows characteristic signals at the following 2-theta values: 3.479; 6.788; 10.043; 16.574; 19.867; 23.180; 29.858.The IR spectrum shows characteristic absorption maxima at [cm"1] 685.6; 818.2; 1008.2; 1032.1; 1052.0; 1065.9; 1106.6; 1122.2; 1167.8; 1180.9; 1215.4; 1279.2; 1320.7; 1379.1; 1421.5; 1466.8; 1497.5; 1605.6; 2850.5; 2918.6; 3027.2; 3070.8; 3189.5; 3258.4; 3447.9. The DSC showes endothermic peaks at 107.42C; 137.69C and 158.68C.The obtained <strong>[162359-55-9]Fingolimod</strong> tosylate form is anhydrous form

Reference： [1]Patent: WO2012/71524,2012,A1 .Location in patent: Page/Page column 19-20

94
[ 98-11-3 ]
[ 162359-55-9 ]
[ 1377321-93-1 ]

Yield	Reaction Conditions	Operation in experiment
	In ethanol; at 20 - 22℃; for 16h;	Example 2: Synthesis of <strong>[162359-55-9]Fingolimod</strong> Besylate5.00 g <strong>[162359-55-9]Fingolimod</strong> free base (16.3 mmol) were dissolved in 100 mL hot ethanol (absolute, >99%) . To this solution were added 2.70g of benzenesulfonic acid (17.1 mmol) in five portions (each 0.54 g). The reaction mixture was allowed to cool to ambient temperature (about 20C to about 22C) and left standing for 16h at the same temperature. After that, the reaction mixture was cooled to -20C and kept at that temperature for additional 24h in order to complete crystallisation. The precipitated crystals were filtrated off at ambienttemperature, washed with cool(about 4C to about 6C) ethanol and dried at 50C for 24h (on normal atmospheric air).Yield: 2.4 g (5.2 mmol)Melting point: 144.7CXRPD showes characteristic signals at the following 2-theta values: 3.219; 6.386; 16.030; 19.272; 25.809; 39.144.The IR spectrum showes characteristic absorption maxima at [cm"1] 610.3; 690.9; 730.5; 753.1; 767.4; 781.1; 819.0; 830.5; 838.6; 890.9; 922.8; 995.7; 1012.9; 1032.1; 1054.9; 1069.5; 1084.1; 1122.3; 1153.9; 1203.7; 1278.2; 1311.4; 1325.8; 1342.6; 1378.8; 1397.6; 1421.5; 1444.5; 1461.7; 1514.8; 1595.5; 2851.3; 2920.9; 2952.8; 2962.2; 3017.0; 3053.4; 3141.1; 3341.1; 3410.9.The DSC showes endothermic peaks at 76.62C; 109.08C and 146.07C.The obtained <strong>[162359-55-9]Fingolimod</strong> besylate form is anhydrous form

Reference： [1]Patent: WO2012/71524,2012,A1 .Location in patent: Page/Page column 20

95
[ 64068-76-4 ]
[ 162359-55-9 ]

Reference： [1]Patent: US2014/170067,2014,A1
[2]Patent: WO2014/111949,2014,A1
[3]Patent: WO2014/111949,2014,A1
[4]Patent: WO2014/111949,2014,A1
[5]Journal of Medicinal Chemistry,2015,vol. 58,p. 3471 - 3484
[6]Patent: WO2013/26765,2013,A1

96
[ 2189-60-8 ]
[ 162359-55-9 ]

Reference： [1]Patent: US2014/170067,2014,A1
[2]Patent: WO2014/111949,2014,A1
[3]Patent: WO2014/111949,2014,A1
[4]Patent: WO2014/111949,2014,A1
[5]Journal of Medicinal Chemistry,2015,vol. 58,p. 3471 - 3484
[6]Patent: WO2013/26765,2013,A1
[7]Chemistry - A European Journal,2018,vol. 24,p. 9535 - 9541

97
[ 268557-49-9 ]
[ 162359-55-9 ]

Reference： [1]Patent: US2014/170067,2014,A1
[2]Patent: WO2014/111949,2014,A1
[3]Patent: WO2014/111949,2014,A1
[4]Patent: WO2014/111949,2014,A1
[5]Journal of Medicinal Chemistry,2015,vol. 58,p. 3471 - 3484
[6]Patent: WO2013/26765,2013,A1

98
[ 162359-55-9 ]
2-amino-2-(fluoromethyl)-4-(4-octylphenyl)butan-1-ol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
2%		FTY 720 (310 mg, 1 .00 mmol) was suspended in dry dichloromethane (10 mL) and cooled down to -78 C. Diethylaminosulfur trifluoride (DAST, 0.13 mL, 1 .00 mmol, 1.0 eq.) was slowly added to this suspension and the mixture was allowed to warm up to r.t. overnight. The reaction was neutralized with saturated sodium bicarbonate solution (30 mL) at -10 C. The phases were separated and the aqueous phase was extracted with dichloromethane (3 x 20 mL). The combined organic layers were dried over MgS04 and the solvent was removed under reduced pressure. The residue was purified by column chromatography (silica gel, 20 x 3 cm, dichloromethane/methanol, 4:1 ) and subsequently by gradient HPLC (RP-HPLC Nucleodur 100-10 Ci8ec column (250 x 16 mm), acetonitrile/water (0.1 % TFA)) with a Knauer HPLC system. The obtained TFA salt was dissolved in methanol (1 mL) and 1 M sodium hydroxide solution (3 mL) and the mixture was extracted with dichloromethane (5 x 5 mL). The organic phases were dried over Na2S04 and concentrated. The product was dried in high vacuum and obtained as highly viscous oil. Yield: 5 mg (2%). 73 1H-NMR (300 MHz, CDCI3) delta [ppm]: 0.87 (t, 3JH,H = 6.7 Hz, 3 H, 19-CH3), 1 .16-1 .37 (m, 10 H, 14-CH2 to I 8-CH2), 1 .56 (m, 2 H, 13-CH2), 1 .81 (m, 2 H, 4-CH2), 2.47-2.68 (m, 4 H, 5-CH2, I 2-CH2), 3.52 (m, 2 H, 1 -CH2), 4.38 (d, 2JH,F = 47.3 Hz, 2 H, 3-CH2), 7.01 -7.1 1 (m, 4 H, 7-CH, 8-CH, 10-CH, 1 1 -CH). 13C-NMR (75 MHz, CDCI3) delta [ppm]: 14.2 (q, C-19), 23.5 (t, C-18), 29.3, 29.4, 29.5, 29.6, 31.7, 32.0, 34.8 (t, C-4, C-5, C-1 3 to C-17), 35.7 (t, C-12), 56.1 (d, 2JC,F = 17.2 Hz, C-2), 65.2 (dt, 3JC,F = 4.1 Hz, C-1 ), 86.1 (dt, 1JC,F = 173.3 Hz, C-3), 128.2, 128.7 (d, C-7, C-8, C-10, C-1 1 ), 138.7, 140.9 (s, C-6, C-9). 19F-NMR (282 MHz, CDCI3) delta [ppm]: -230.3 (t, 2JKF = 47.3 Hz, 1 F, 3-CH2F). Exact mass (ESI+): Ci9H32FNO + H+: calcd. 310.2541 , found 310.2542; Ci9H32FNO + Na+: calcd. 332.2360, found 332.2379.
2%	With diethylamino-sulfur trifluoride; In dichloromethane; at -78 - 20℃;	2-Amino-2-(fluoromethyl)-4-(4-octylphenyl)butan-1-ol (SSS 461) FTY 720 (310 mg, 1.00 mmol) was suspended in dry dichloromethane (10 mL) and cooled down to -78 C. Diethylaminosulfur trifluoride (DAST, 0.13 mL, 1.00 mmol, 1.0 eq.) was slowly added to this suspension and the mixture was allowed to warm up to r.t. overnight. The reaction was neutralized with saturated sodium bicarbonate solution (30 mL) at -10 C. The phases were separated and the aqueous phase was extracted with dichloromethane (320 mL). The combined organic layers were dried over MgSO4 and the solvent was removed under reduced pressure. The residue was purified by column chromatography (silica gel, 203 cm, dichloromethane/methanol, 4:1) and subsequently by gradient HPLC (RP-HPLC Nucleodur 100-10 C18ec column (25016 mm), acetonitrile/water (0.1% TFA)) with a Knauer HPLC system. The obtained TFA salt was dissolved in methanol (1 mL) and 1 M sodium hydroxide solution (3 mL) and the mixture was extracted with dichloromethane (55 mL). The organic phases were dried over Na2SO4 and concentrated. The product was dried in high vacuum and obtained as highly viscous oil. Yield: 5 mg (2%). 1H-NMR (300 MHz, CDCl3) delta [ppm]: 0.87 (t, 3JH,H=6.7 Hz, 3H, 19-CH3), 1.16-1.37 (m, 10H, 14-CH2 to 18-CH2), 1.56 (m, 2H, 13-CH2), 1.81 (m, 2H, 4-CH2), 2.47-2.68 (m, 4H, 5-CH2, 12-CH2), 3.52 (m, 2H, 1-CH2), 4.38 (d, 2JH,F=47.3 Hz, 2H, 3-CH2), 7.01-7.11 (m, 4H, 7-CH, 8-CH, 10-CH, 11-CH). 13C-NMR (75 MHz, CDCl3) delta [ppm]: 14.2 (q, C-19), 23.5 (t, C-18), 29.3, 29.4, 29.5, 29.6, 31.7, 32.0, 34.8 (t, C-4, C-5, C-13 to C-17), 35.7 (t, C-12), 56.1 (d, 2JC,F=17.2 Hz, C-2), 65.2 (dt, 3JC,F=4.1 Hz, C-1), 86.1 (dt, 1JC,F=173.3 Hz, C-3), 128.2, 128.7 (d, C-7, C-8, C-10, C-11), 138.7, 140.9 (s, C-6, C-9). 19F-NMR (282 MHz, CDCl3) delta [ppm]: -230.3 (t, 2JH,F=47.3 Hz, 1F, 3-CH2F). Exact mass (ESI+): C19H32FNO+H+: calcd. 310.2541, found 310.2542; C19H32FNO+Na+: calcd. 332.2360, found 332.2379.

Reference： [1]Journal of Medicinal Chemistry,2015,vol. 58,p. 3471 - 3484
[2]Patent: WO2013/26765,2013,A1 .Location in patent: Page/Page column 67-68
[3]Patent: US2014/170067,2014,A1 .Location in patent: Paragraph 0508; 0509; 0510; 0511; 0512

99
[ 2767-70-6 ]
[ 162359-55-9 ]

Reference： [1]Tetrahedron,2013,vol. 69,p. 2927 - 2932

100
[ 1427308-40-4 ]
[ 162359-55-9 ]

Reference： [1]Tetrahedron,2013,vol. 69,p. 2927 - 2932

101
[ 1427308-41-5 ]
[ 162359-55-9 ]

Reference： [1]Tetrahedron,2013,vol. 69,p. 2927 - 2932

102
[ 1427308-22-2 ]
[ 162359-55-9 ]

Reference： [1]Tetrahedron,2013,vol. 69,p. 2927 - 2932

103
[ 1427308-50-6 ]
[ 162359-55-9 ]

Reference： [1]Tetrahedron,2013,vol. 69,p. 2927 - 2932

104
[ 928165-59-7 ]
[ 162359-55-9 ]

Reference： [1]Patent: US2014/235895,2014,A1
[2]Patent: US2014/235895,2014,A1

105
[ 1674-37-9 ]
[ 162359-55-9 ]

Reference： [1]Patent: WO2014/111949,2014,A1
[2]Patent: WO2014/111949,2014,A1
[3]Patent: WO2014/111949,2014,A1
[4]Patent: US2014/235895,2014,A1
[5]Patent: US2014/235895,2014,A1

106
[ 10541-56-7 ]
[ 162359-55-9 ]

Reference： [1]Patent: WO2014/111949,2014,A1
[2]Patent: WO2014/111949,2014,A1
[3]Patent: WO2014/111949,2014,A1

107
N-[1,4-dihydroxy-2-(hydroxymethyl)-4-(4-octylphenyl)butan-2-yl]acetamide [ No CAS ]
[ 162359-55-9 ]

Reference： [1]Patent: WO2014/111949,2014,A1
[2]Patent: WO2014/111949,2014,A1
[3]Patent: WO2014/111949,2014,A1

108
[ 1620230-20-7 ]
[ 162359-55-9 ]

Reference： [1]Patent: WO2014/111949,2014,A1

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
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CAS No. :	162359-55-9	MDL No. :	MFCD14705150
Formula :	C₁₉H₃₃NO₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	-
M.W :	307.47	Pubchem ID :	-
Synonyms :	FTY720 free base;FTY-720;FTY720 (free base);FTY-720A	Chemical Name :	2-Amino-2-(4-octylphenethyl)propane-1,3-diol

Num. heavy atoms :	22
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.68
Num. rotatable bonds :	12
Num. H-bond acceptors :	3.0
Num. H-bond donors :	3.0
Molar Refractivity :	94.32
TPSA :	66.48 Å²

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	Yes
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	Yes
CYP3A4 inhibitor :	Yes
Log Kp (skin permeation) :	-5.22 cm/s

Log Po/w (iLOGP) :	3.76
Log Po/w (XLOGP3) :	4.16
Log Po/w (WLOGP) :	3.2
Log Po/w (MLOGP) :	3.01
Log Po/w (SILICOS-IT) :	4.62
Consensus Log Po/w :	3.75

[ CAS No. 162359-55-9 ] {[proInfo.proName]}

Quality Control of [ 162359-55-9 ]

Related Doc. of [ 162359-55-9 ]

Product Details of [ 162359-55-9 ]

Calculated chemistry of [ 162359-55-9 ] Expand+

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 162359-55-9 ]

Application In Synthesis of [ 162359-55-9 ]

[ 162359-55-9 ] Synthesis Path-Downstream 1~108

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Lipinski :	0.0
Ghose :	None
Veber :	1.0
Egan :	0.0
Muegge :	0.0
Bioavailability Score :	0.55

Log S (ESOL) :	-3.78
Solubility :	0.0514 mg/ml ; 0.000167 mol/l
Class :	Soluble
Log S (Ali) :	-5.26
Solubility :	0.00167 mg/ml ; 0.00000544 mol/l
Class :	Moderately soluble
Log S (SILICOS-IT) :	-5.76
Solubility :	0.000532 mg/ml ; 0.00000173 mol/l
Class :	Moderately soluble

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	2.0
Synthetic accessibility :	2.27

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P280-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302	Packing Group:	N/A
GHS Pictogram:

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