Name: 66605-57-0|Boc-Phenylalaninol|98%
Brand: Ambeed
SKU: A102712
Price: 5.0 USD
Availability: InStock
Rating: 97 (35 reviews)

1
[ 5930-92-7 ]
[ 66605-57-0 ]
ethyl 1-<3-phenyl-2-tert-butoxycarbonylaminopropyl>-4-nitropyrrole-2-carboxylate [ No CAS ]

Reference： [1]Tetrahedron,1993,vol. 49,p. 5831 - 5844

2
[ 691-64-5 ]
[ 3182-95-4 ]
[ 66605-57-0 ]

Yield	Reaction Conditions	Operation in experiment
80%	With sodium hydrogencarbonate In 1,4-dioxane; water Ambient temperature;

Reference： [1]Rubini, E.; Gilon, C.; Selinger, Z.; Chorev, M. [Tetrahedron, 1986, vol. 42, # 21, p. 6039 - 6045]

3
[ 24424-99-5 ]
[ 3182-95-4 ]
[ 66605-57-0 ]

Yield	Reaction Conditions	Operation in experiment
100%	In dichloromethane
100%	In ethanol at 20℃;
100%	In water at 30 - 35℃; for 1h;

100%	With sodium hydrogencarbonate In tetrahydrofuran; water at 25℃; for 10h; Inert atmosphere;
99%	In acetonitrile at 20℃; for 3h;
99%	In tetrahydrofuran for 16h;	16 Example 16 [00212] AMD8777: Preparation of N-(2-pyridinylmethyl)-N'-[(2-amino-3-phenyl)propyl]-N'-(5,6,7,8-tetrahydro-8-quinolinyl)-1,4-benzenedimethanamine (hydrobromide salt). To a solution of L-Phenylalaninol (358 mg, 2.37 mmol) in wet THF (5 mL) was added di-t-butyl dicarbonate (715 mg, 3.28 mmol). The mixture was stirred for 16 hours then concentrated in vacuo. Purification of the crude product by column chromatography on silica gel (hexanes/EtOAc, 3:1) afforded the N-Boc-protected alcohol (590 mg, 99%) as a white solid: 1H NMR (CDCl3) δ 1.41 (br s, 9H), 2.45 (br s, 1H), 2.84 (d, 2H, J=6.0 Hz), 3.52-3.58 (m, 1H), 3.65-3.70 (m, 1H), 3.85-3.88 (br m, 1H), 4.76 (br s, 1H), 7.20-7.34 (m, 5H).
98%	With sodium hydrogencarbonate In dichloromethane; water at 20℃; for 3h;	1.a Saturated NaHC03 aqueous solution (3 mL) was added to a solution of (-)- phenylalaninol (1.007 g, 6.66 mmol) and di-t-butyl dicarbonate (2.18 g, 9.99 mmol) in CH2Ci2 and the resulting mixture was stirred at room temperature for 3 h. The reaction was complete indicated by TLC. The organic layer was separated and the aqueous layer was extracted with CH2Ci2 (2 times). The combined the organic layers were dried (Na2SO4), concentrated, and the residue was purified by flash column chromatography (hexane/EtOAc 3: 1) to give a white solid (1.64 g, 98%).
96%	With triethylamine In tetrahydrofuran at 0 - 20℃; for 1.5h; Inert atmosphere;	(S)-f-Butyl (1-hydroxy-3-phenylpropan-2-yl)carbamate (6a) To a solution of phenyl alaninol (5a, 6.04 g, 40.0 mmol, 1.00 eq.) and triethyl amine (5.56 ml, 40.0 mmol, 1.00 eq.) in THF (120 ml), Boc-anhydride (8.72 g, 40 mmol, 1.00 eq) was added at 0 °C. The reaction mixture was warmed to room temperature and stirred for 1.5 h. Afterwards the solvent was removed in high vacuum and the residue dissolved in EtOAc (100 ml). The organic phase was washed with water (2 x 100 ml) and brine (1 x 100 ml). After drying over MgS04 the solvent was removed at reduced pressure toS2yield the desired Boc-protected aminoalcohol as a colorless solid (9.55 g, 96%). The analytical data matched the literature values.'
95%	In tetrahydrofuran; water for 1h; Ambient temperature;
95%	In tetrahydrofuran; water at 20℃; for 1h;
95%	With sodium hydroxide In tetrahydrofuran at 20℃; for 12h;
95%	With N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 0 - 20℃; for 6h; Inert atmosphere;	2.1 2.2.1 Syntheses of Boc-amino alcohol General procedure: (Boc)2O (2.10 g, 12 mmol) was added to a solution of amino alcohol (10 mmol) and diisopropylethylamine (DIPEA) (1.44 g, 12 mmol) in THF(40 mL) under N2 protection at 0 °C. The mixture was stirred for 6 h at room temperature, then the solvent was removed under reduced pressure and the resulting residue was dissolved in 100 mL ethyl acetate. This solution was washed twice with 100 mL of water, once with 100 mL of saturated aqueous sodium chloride, dried over Na2SO4 and concentrated under reduced pressure to give product L-3 or L-4 as yellow oil. L-4: 2.38g, yield 95%; [α]20D[α]D20=-20.8 (c 0.05, CHCl3); 1H NMR(CDCl3): δ 7.36-7.21 (m, 5H), 4.71 (s, 1H), 3.87 (s, 1H), 3.66-3.55 (m, 2H), 2.84 (d, J=7.8Hz, 2H), 2.23 (s, 1H), 1.41 (s, 9H).
95%	With N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 0 - 20℃; for 6h; Inert atmosphere;	2.1 General procedure: (Boc)2O (2.10 g, 12 mmol) was added to a solution of amino alcohol (10 mmol) and diisopropylethylamine (DIPEA) (1.44 g, 12 mmol) in THF(40 mL) under N2 protection at 0 °C. The mixture was stirred for 6 h at room temperature, then the solvent was removed under reduced pressure and the resulting residue was dissolved in 100 mL ethyl acetate. This solution was washed twice with 100 mL of water, once with 100 mL of saturated aqueous sodium chloride, dried over Na2SO4 and concentrated under reduced pressure to give product L-3 or L-4 as yellow oil. L-4: 2.38 g, yield 95%; = -20.8 (c 0.05, CHCl3); 1H NMR(CDCl3): δ 7.36-7.21 (m, 5H), 4.71 (s, 1H), 3.87 (s, 1H), 3.66-3.55 (m, 2H), 2.84 (d, J = 7.8 Hz, 2H), 2.23 (s, 1H), 1.41 (s, 9H).
95%	In dichloromethane at 0 - 25℃; for 12h; Inert atmosphere;	1; 3.2.8 (S)- 1 -Methoxy-3-phenylpropan-2-amine (23) ffl-Tert-butvH 1 -hvdroxy-3-phenylpropan-2- vPcarbamate (21) To a solution, under argon and at 0°C, of 2.00 g (13.2 mmol, 1 eq.) of (S)-2-amino-3- phenylpropan-l-ol in 40 mL of anhydrous CH2CI2were added 3.63 mL (3.48 g, 15.8 mmol, 1.2 eq.) of di-iert-butyl dicarbonate. The solution was stirred at 25°C for 12 h, washed with 50 mL of a 10% aqueous acetic acid solution and with 40 mL of brine. The organic layer was dried over Na2S04, filtered and concentrated in vacuo. The residue was purified by flash chromatography (cyclohexane / AcOEt 2: 1) to afford 3.15 g of 21 as a white solid were obtained. Yield: 95%; NMR 1H (400 MHz, CDC13): δ 1.41 (9H, s), 2.78- 2.90 (m, 2H), 3.61 [AB(ABX), J = 11.0 Hz, J = 5.3 Hz, J = 3.8 Hz, 2H], 3.87 (sbr, 1H), 4.77 (sbr, 1H), 7.20-7.26 (m, 3H), 7.28-7.32 (m, 2H) ppm; NMR13C (100 MHz, CDC13): δ 28.3, 37.5, 53.8, 64.3, 79.7, 126.5, 128.5, 129.3, 137.8, 156.1 ppm; IR Vmax: 3346, 2934, 1681, 1447, 1314, 1259 cm"1; MS (ESI+) m/z: 252 (M + H)+; [ ]D2°: -15.9° (c 0.1; AcOEt).
95%	In dichloromethane at 0 - 25℃; for 12h; Inert atmosphere;	4.1.1.1. (S)-Tert-butyl-(1-hydroxy-3-phenylpropan-2-yl)carbamate(31). To a solution, under argon and at 0 C, of (S)-2-amino-3-phenylpropan-1-ol (2.00 g, 13.2 mmol, 1 eq.) in 40 mL of anhydrousCH2Cl2 was added di-tert-butyl dicarbonate (3.48 g,15.8 mmol, 1.2 eq.). The solution was stirred at 25 C for 12 h,washed with 50 mL of a 10% aqueous acetic acid solution and with40 mL of brine. The organic layer was dried over Na2SO4, filteredand concentrated in vacuo. The residue was purified by flashchromatography (Cyclohexane/AcOEt 2:1) to afford 31 as a whitesolid. Yield: 95%. Rf 0.45 (Cyclohexane/AcOEt 2:1). a20D - 16 (c 0.1,AcOEt). Mp 90.4e92.0 C. 1H NMR (400 MHz, CDCl3) d 7.29e7.18 (m,5H), 3.80e3.75 (m, 1H), 3.50 (d, J 5.2 Hz, 2H), 2.89 (dd, J 13.6,6.0 Hz, 1H), 2.68 (dd, J 13.2, 8.0 Hz, 1H), 1.39 (s, 9H). 13C NMR(100 MHz, CDCl3) d 156.9, 138.8, 129.0, 127.9, 125.8, 80.1, 64.7, 55.5,38.6, 28.7. IR √max: 3346, 2934, 1681, 1447, 1314, 1259 cm1. MS(ESI) m/z: 252 (M H). HRMS calcd for C14H21NO3Na (M Na),274.1419 found 274.1420.
93%	With sodium hydrogencarbonate In 1,4-dioxane; water at 0℃; for 12h;
92%	In water at 30 - 35℃; for 0.333333h;
90%	With triethylamine In tetrahydrofuran for 2h;
90%	With zirconium(IV) chloride In acetonitrile at 20℃; for 0.0833333h;
90%	With indium(III) bromide at 30 - 35℃; for 0.25h;
90%	With perchloric acid at 30 - 35℃; for 0.25h;
90%	With 1-methylimidazolium tetrafluoroborate at 30 - 35℃; for 0.25h;
89%	With triethylamine In dichloromethane at 20℃; for 18h;
88%	In chloroform at 0 - 20℃;
87%	With triethylamine In N,N-dimethyl-formamide at 0℃; for 1h;
87%	With zinc(II) perchlorate In dichloromethane at 20℃; for 43h;
87%	In acetonitrile at 20℃; for 4h;
84%	With sodium hydroxide In tetrahydrofuran; water at 0 - 20℃; for 18h;	8.1 (1) To a solution of L-phenylalaninol (50 g, 66 mmol) in tetrahydrofuran (1.3 L) and water (630 mL), a solution of di-t-butyl dicarbonate (140 g, 0.67 mol) in tetrahydrofuran (500 mL) and 1M NaOH (660 mL) were added slowly at the same time under ice-cooled condition. The mixture was stirred at room temperature for 18 hours, concentrated in vacuo, and diluted with ethyl acetate (EtOAc) (1 L). The solution was washed with 1M HC1, saturated aq. NaHC03 and saturated aq. NaCl, dried over anhydrous MgS04, and concentrated in vacuo. The resulting whitesolidwasrecrystalizedfromethylacetate/hexane (1: 10). The crystal was filtered off to give N- (tert-butoxycarbonyl)- L-phenylalaninol (70 g, 84%) as colorless crystals.
84%	In tetrahydrofuran; hexane; water; ethyl acetate	R.8.1 (3S)-3-Amino-N-ethyl-2-hydroxy-4-phenylbutanamide hydrochloride (1) A solution of di-t-butyldicarbonate (140 g, 0.67 mol) in tetrahydrofuran (500 mL) and a 1M aqueous sodium hydroxide solution (660 mL) were simultaneously and slowly added to a solution of L-phenylalaninol (50 g, 66 mmol) in tetrahydrofuran (1.3 L) and water (630 mL) under ice-cold conditions. This solution was stirred at room temperature for 18 hours, and the organic solvent was distilled off in vacuo, after which ethyl acetate (1 L) was added thereto. This solution was washed with 1M hydrochloric acid, saturated aqueous sodium hydrogen carbonate solution, and saturated saline solution, dehydrated with anhydrous magnesium sulfate, and concentrated in vacuo. The obtained white solid was recrystallized from a liquid mixture of ethyl acetate/hexane (1:10), thereby yielding N-(tert-butoxycarbonyl)-L-phenylalaninol (70 g, 84%) as a colorless crystal.
84%	With sodium hydroxide In tetrahydrofuran; water at 20℃; for 18h; Cooling with ice;	8.1 (b)A solution of di-t-butyldicarbonate (140 g, 0.67 mol) in tetrahydroffiran (500 mE) and a 1M aqueous sodium hydrox40 ide solution (660 mE) were simultaneously and slowly addedto a solution of E-phenylalaninol (50 g, 66 mmol) in tetrahydrofuran (1.3 E) and water (630 mE) under ice-cold conditions. This solution was stirred at room temperature for 18 hours, and the organic solvent was distilled off in vacuo, after45 which ethyl acetate (1 E) was added thereto. This solutionwas washed with 1 M hydrochloric acid, saturated aqueous sodium hydrogen carbonate solution, and saturated saline solution, dehydrated with anhydrous magnesium sulfate, and concentrated in vacuo. The obtained white solid was recrys50 tallized from a liquid mixture of ethyl acetate/hexane (1:10),thereby yielding N-(tert-butoxycarbonyl)-E-phenylalaninol (70 g, 84%) as a colorless crystal.
84%	With sodium hydroxide In tetrahydrofuran; water at 20℃; for 18h; Cooling with ice;	R.8.1 (3S)-3-Amino-N-ethyl-2-hydroxy-4-phenylbutanamide hydrochloride (1) A solution of di-t-butyldicarbonate (140 g, 0.67 mol) in tetrahydrofuran (500 mL) and a 1M aqueous sodium hydroxide solution (660 mL) were simultaneously and slowly added to a solution of L-phenylalaninol (50 g, 66 mmol) in tetrahydrofuran (1.3 L) and water (630 mL) under ice-cold conditions. This solution was stirred at room temperature for 18 hours, and the organic solvent was distilled off in vacuo, after which ethyl acetate (1 L) was added thereto. This solution was washed with 1M hydrochloric acid, saturated aqueous sodium hydrogen carbonate solution, and saturated saline solution, dehydrated with anhydrous magnesium sulfate, and concentrated in vacuo. The obtained white solid was recrystallized from a liquid mixture of ethyl acetate/hexane (1:10), thereby yielding N-(tert-butoxycarbonyl)-L-phenylalaninol (70 g, 84%) as a colorless crystal.
82%	With sodium hydroxide In tetrahydrofuran; water at 0 - 20℃; for 16h;
78%	With iodine at 20℃; for 2.5h;
76%	With sodium carbonate In methanol at 20℃; for 10h;	51.B-2 Step B-2Tert-butyl (1-hydroxy-3-phenyl-2-yl) carbamatePreparation 3 Intermediate 2 (2.5g, 15.92mmol) was dissolved 30mlMeOH added (Boc) 2O (3.9,17.89mmol), Na2CO3 (7,66.04mmol), stirred at room temperature 10H, Completed the the reaction, the solvent was distilled off, water was added to precipitate The solid filtration, the filter cake washed with water, and dried. To give a white solid 3.04g, yield 76%,
67%	In ethanol at 20℃; for 0.833333h;
	In chloroform for 4h; Yield given;
	With triethylamine In N,N-dimethyl-formamide a) 0 deg C, 30 min, b) RT, 2 h; Yield given;
	With TEA In tetrahydrofuran for 1h; Ambient temperature; Yield given;
	In tetrahydrofuran for 18h; Ambient temperature;
	In tetrahydrofuran Ambient temperature;
	In tetrahydrofuran; water for 17h;
3.52 g	In dichloromethane at 60℃; for 6h;
	In acetonitrile at 20℃; for 3h;
	With sodium hydroxide at 25℃; for 12h;
	In dichloromethane
0.1 g	With triethylamine In dichloromethane at 0℃; for 1h;
	In tetrahydrofuran	R.12 (2S)-2-(tert-Butoxycarbonyl)amino-3-phenyl-1-propanol (Reference compound No. 12-1) Reference Example 12 (2S)-2-(tert-Butoxycarbonyl)amino-3-phenyl-1-propanol (Reference compound No. 12-1) A solution of di-tert-butyl dicarbonate (1.44 g) in tetrahydrofuran is added dropwise to a solution of (S)-2-amino-3-phenyl-1-propanol (1.00 g) in tetrahydrofuran (15 ml), and the mixture is stirred for 30 minutes. Then, the reaction mixture is concentrated under reduced pressure, and the resulting residue is purified by silica gel column chromatography to give 1.70 g of the titled reference compound. mp 95.2-96.7° C.; [α] D20 -26.9° (c=1.0, methanol); IR(KBr,cm-1): 3355,1688,1529,1444,1367,1316,1270,1252,1169, 1006,702.
	In dichloromethane; Petroleum ether	34.a a a (2S)-2-t-Butyloxycarbonylamino-3-phenyl-1-propanol To a solution of L-Phenylalaninol (3.52 g) in dichloromethane (35 ml) was added di-t-butyldicarbonate (5.09 g). After 16h the solvent was removed in vacuo and the residue chromatographed on silica gel (eluding with 10-20% ethyl acetate in petroleum ether to give the title compound.
4.82 g (19.2 mmol, 96%)	In tetrahydrofuran	1 Chart (B-1 to B-2) PREPARATION 1 Nα-tert-Butyloxycarbonyl-L-phenylalaninol Chart (B-1 to B-2) To a stirred solution of 3.024 g (20 mmol) of L-phenylalaninol in 50 ml of dry tetrahydrofuran at 0° C. under argon is added 4.8 g 922 mmol of di-tert-butyl dicarbonate. After stirring at room temperature for 3 hrs, the reaction mixture is then concentrated to give 4.82 g (19.2 mmol, 96%) of the titled alcohol. 1 H-NMR (CDCl3): δ 1.48, 2.74, 7.25, C#1#4H21 NO3: Calcd.: C, 66.91; H, 8.42; N, 5.57. Found: C, 66.62; H, 8.35; N, 5.47. IR (mull): 3360, 2925, 1685, 1530, and 1005. [α]D (CHCl3; C=8.795 mg/ml)-24°.
	With triethylamine In tetrahydrofuran at 0 - 20℃;
	With triethylamine In dichloromethane
	In ethyl acetate for 1.5h;
	With triethylamine In dichloromethane at 20℃;
	With triethylamine In dichloromethane at 0 - 20℃;
	In dichloromethane at 0 - 20℃; for 1h; Inert atmosphere;
58 g	In dichloromethane at 5 - 25℃; for 1h;
	In dichloromethane at 0 - 20℃; for 1h;
	With triethylamine In dichloromethane at 0 - 20℃; Inert atmosphere; Glovebox; Schlenk technique;
	In dichloromethane at 20℃;
47 mg	With dmap; triethylamine In dichloromethane for 5h;
	In neat (no solvent) at 20℃; Sonication; Green chemistry;	General procedure for N-tert-butoxycarbonylation ofβ-amino alcohols 3(a-c) General procedure: (S)-amino alcohols (1 mmol) and di-tert-butyl dicarbonate [(Boc)2O, 1.1 mmol] were placed in a glass tube under neat conditions and were sonicated for a suitable time. After completion of the reaction (as indicated by TLC), 5 mL of diethyl ether was added to the mixture, the resulting tert-butanol was freely soluble in diethyl ether and the N-Boc product was crystallized.
	With triethylamine In dichloromethane Cooling;	Preparation of (S)-4-benzyloxazolidin-2-one 7. To a stirred suspension of LiAlH4 (11.5 g, 5 eq, 0.3 mol) in dry THF (200 mL) at 0 °C was added portionally L-phenylalanine (10 g, 61 mmol). The mixture was heated at reflux for 3 h and then cooled to 0 °C. The mixture was then treated dropwise with 10% aqueous sodium hydroxide (18 mL). The mixture was filtered, washed with THF. To the precipitate THF was added and the mixture was additionally refluxed for 1 h and then filtered. Combined filtrate was evaporated under reduced pressure to give 8.15 g (89%) of the L-phenylalaninol as a colorless solid. To a cooled solution of the 3 g (19.9 mmol) of aminoalcohol in dichloromethane (20 mL) NEt3 (2.1 g, 20.8 mmol) was added followed by ditretbutyldicarbonate (4.53 g, 20.8 mmol). The mixture was stirred overnight and then washed with brine, water. The combined organic phase was dried over Na2SO4, and concentrated under reduced pressure to obtained Boc-protected L-phenylalaninol with quantitative yield. Crude product (4.67 g, 19.9 mmol) was dissolved in THF (20 mL) and cooled to 0 °C. Thionyl chloride (11.5 ml, 8 eq) was then added dropwise and the mixture was stirred for 3 h. After that, reaction mixture was diluted with ether and then washed with brine, water and dried over Na2SO4. The solvents were evaporated under reduced pressure. The residue was purified by flash chromatography (hexane/EtOAc (3:1 to 1:1) to give 2.98 g (85%) of (S)-4-benzyloxazolidin-2-one 7 as colorless crystals. mp - 86-87°C; [α]D28 = -63.2 (C 1, CHCl3); 1H NMR (300 MHz, CDCl3): δ 7.38-7.26 (m, 3H), 7.21-7.18 (m, 2H), 6.04 (br.s, 1H), 4.44 (t, J = 8.0 Hz, 1H), 4.19-4.07 (m, 2H), 2.92-2.88 (m, 2H).
	In acetonitrile at 0℃; for 6h;
	In water at 35℃; for 1h;
	With triethylamine In dichloromethane	4.3. General procedure for the synthesis of intermediates (10a-g) General procedure: L-amino alcohol (1 equiv), (Boc)2O (1.2 equiv) and trimethylamine(2 equiv) were added to dichloromethane. The mixture wasstirred under ice bath conditions. The reactionwas followed by TLCand diluted with dichloromethane. The organic phase was washedwith citric acid (1 N) and saturated NaHCO3 then dried over Na2SO4and filtered. The filtrate was concentrated and purified by a silicacolumn to afford compounds 10a-g.
	With triethylamine In dichloromethane
	With sodium hydroxide In dichloromethane at 20℃; for 24h;	Synthesis of (S)-tert-butyl (1-hydroxy-3-phenylpropan-2-yl)carbamate2 2 A solution of tert-butyl dicarbonate (1eq, 6.7mmol) in DCM (14 mL) was added dropwise to a solution of(S)-2-amino-3-phenylpropan-1-ol (1) (1eq, 6.7mmol) in a mixture of DCM (14 mL) and 1N NaOH (11mL). The reaction mixture was then stirred at room temperature for 24 h, and the organic phase wasseparated. The aqueous layer was extracted with DCM (10 mL x 2). The combined organic layers werewashed with water (10 mL x 1) and dried over Na2SO4. The solvent was evaporated in vacuo, to afford(S)-tert-butyl (1-hydroxy-3-phenylpropan-2-yl)carbamate (2) as a white solid; the crude has been usedwithout further purification in the following synthetic cascade. All analytical data are in agreement withliterature.
141 mg	In acetonitrile at 0 - 20℃; for 24h;
	With triethylamine In methanol; dichloromethane at 23℃; for 2h;	General method for the synthesis of B2b-e General procedure: Compound B1b-e (10 mmol) was dissolved in amixture of CH2Cl2:CH3OH (1:5; 1 M) andtriethylamine (1.2 mmol) was added. Di-tert-butyl dicarbonate (12 mmol) wasdissolved in dichloromethane (0.8 M, 15 mL) and added slowly to the reactionmixture. The resulting reaction was stirred at 23C for 2 h, followed by TLC analysis that showeda full consumption of the starting material. The reaction mixture wasevaporated under reduced pressure, and the residue was purified by columnchromatography, then dried on high vacuum to yield B2b-e (92-98 % yield).
	With triethylamine In dichloromethane at 0 - 20℃; Inert atmosphere;
	With triethylamine In methanol; dichloromethane at 23℃; for 2h;
	With triethylamine In dichloromethane at 20℃; for 6h;	4.3 The procedure for the synthesis of the intermediates (3a, b) General procedure: The intermediates (2a, b;1.0 equiv) was added to the mixture solution of (Boc)2O (1.5 equiv) and TEA (2.5 equiv) at room temperature. The mixture solution was reacted for 6h. After the reaction completion as monitored by TLC. Then, the solution was poured into ice-water and extracted with dichloromethane, the organic phase was dried overnight with anhydrous sodium sulfate. Finally, the desired intermediates (3a, b) were obtained under vacuum distillation.

Reference： [1]Christoffers, Jens; Mann, Alexander [Angewandte Chemie - International Edition, 2000, vol. 39, # 15, p. 2752 - 2754]
[2]Delcamp, Jared H.; Brucks, Alexandria P.; White, M. Christina [Journal of the American Chemical Society, 2008, vol. 130, # 34, p. 11270 - 11271]
[3]Kerherve, Jennifer; Botuha, Candice; Dubois, Joelle [Organic and Biomolecular Chemistry, 2009, vol. 7, # 10, p. 2214 - 2222]
[4]Cao, Meiqun; Li, Yinghong; Long, Bohua; Tao, Cheng; Wu, Zhengzhi; Zeng, Xiaobin [Organic and biomolecular chemistry, 2020, vol. 18, # 28, p. 5349 - 5353]
[5]Lewanowicz; Lipinski; Siedlecka; Skarzewski; Baert [Tetrahedron, 1998, vol. 54, # 23, p. 6571 - 6586]
[6]Current Patent Assignee: SANOFI - US6750348, 2004, B1 Location in patent: Page column 44
[7]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2005/85227, 2005, A1 Location in patent: Page/Page column 76
[8]Ebner, Christian; Pfaltz, Andreas [Tetrahedron, 2011, vol. 67, # 52, p. 10287 - 10290]
[9]Rama Rao [Tetrahedron Letters, 1995, vol. 36, # 14, p. 2505 - 2508]
[10]Gurjar, Mukund K.; Pal, Shashwati; Rama Rao; Pariza, Richard J.; Chorghade, Mukund S. [Tetrahedron, 1997, vol. 53, # 13, p. 4769 - 4778]
[11]Hunter, Christopher; Jackson, Richard F. W.; Rami, Harshad K. [Journal of the Chemical Society. Perkin Transactions 1 (2001), 2000, # 2, p. 219 - 223]
[12]Li, Qian; Xu, Kuoxi; Song, Pan; Dai, Yanpeng; Yang, Li; Pang, Xiaobin [Dyes and Pigments, 2014, vol. 109, p. 169 - 174]
[13]Li, Qian; Xu, Kuoxi; Song, Pan; Dai, Yanpeng; Yang, Li; Pang, Xiaobin [Dyes and Pigments, 2014, vol. 109, p. 163 - 168]
[14]Current Patent Assignee: CENTRE HOSPITALIER UNIVERSITAIRE D'AMIENS-PICARDIE; CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE; UNIVERSITY OF PICARDIE JULES VERNE - WO2019/86614, 2019, A1 Location in patent: Page/Page column 45; 73; 74
[15]Dassonville-Klimpt; Schneider; Damiani; Tisnerat; Cohen; Azas; Marchivie; Guillon; Mullié; Agnamey; Totet, Anne; Dormoi; Taudon; Pradines; Sonnet [European Journal of Medicinal Chemistry, 2022, vol. 228]
[16]Duddu; Eckhardt; Furlong; Knoess; Berger; Knochel [Tetrahedron, 1994, vol. 50, # 8, p. 2415 - 2432]
[17]Chankeshwara, Sunay V.; Chakraborti, Asit K. [Organic Letters, 2006, vol. 8, # 15, p. 3259 - 3262]
[18]Caputo, Romualdo; Cassano, Ersilia; Longobardo, Luigi; Palumbo, Giovanni [Tetrahedron, 1995, vol. 51, # 45, p. 12337 - 12350]
[19]Sharma; Janardhan Reddy; Sree Lakshmi; Radha Krishna, Palakodety [Tetrahedron Letters, 2004, vol. 45, # 37, p. 6963 - 6965]
[20]Chankeshwara, Sunay V.; Chakraborti, Asit K. [Synthesis, 2006, # 16, p. 2784 - 2788]
[21]Chakraborti, Asit K.; Chankeshwara, Sunay V. [Organic and Biomolecular Chemistry, 2006, vol. 4, # 14, p. 2769 - 2771]
[22]Sunitha, Sadula; Kanjilal, Sanjit; Reddy, P. Srinivasa; Prasad, Rachapudi B.N. [Tetrahedron Letters, 2008, vol. 49, # 16, p. 2527 - 2532]
[23]Mansueto, Markus; Frey, Wolfgang; Laschat, Sabine [Chemistry - A European Journal, 2013, vol. 19, # 47, p. 16058 - 16065]
[24]Quagliato, Dominick A.; Andrae, Patrick M.; Matelan, Edward M. [Journal of Organic Chemistry, 2000, vol. 65, # 16, p. 5037 - 5042]
[25]Ohno, Hiroaki; Toda, Ayako; Takemoto, Yoshiji; Fujii, Nobutaka; Ibuka, Toshiro [Journal of the Chemical Society. Perkin transactions I, 1999, # 20, p. 2949 - 2962]
[26]Bartoli, Giuseppe; Bosco, Marcella; Locatelli, Manuela; Marcantoni, Enrico; Massaccesi, Massimo; Melchiorre, Paolo; Sambri, Letizia [Synlett, 2004, # 10, p. 1794 - 1798]
[27]Braga, Antonio L.; Luedtke, Diogo S.; Paixao, Marcio W.; Alberto, Eduardo E.; Stefani, Helio A.; Juliano, Luiz [European Journal of Organic Chemistry, 2005, # 20, p. 4260 - 4264]
[28]Current Patent Assignee: SENJU PHARMACEUTICAL CO.,LTD. - WO2005/56519, 2005, A1 Location in patent: Page/Page column 32
[29]Current Patent Assignee: OSAKA CITY UNIVERSITY - EP2647386, 2013, A1 Location in patent: Page/Page column
[30]Current Patent Assignee: OSAKA CITY UNIVERSITY - US9371359, 2016, B2 Location in patent: Page/Page column 34
[31]Current Patent Assignee: OSAKA CITY UNIVERSITY; SENJU PHARMACEUTICAL CO.,LTD. - US2019/314320, 2019, A1 Location in patent: Paragraph 0184
[32]Haghshenas, Pouyan; Gravel, Michel [Organic Letters, 2016, vol. 18, # 18, p. 4518 - 4521]
[33]Varala, Ravi; Nuvula, Sreelatha; Adapa, Srinivas R. [Journal of Organic Chemistry, 2006, vol. 71, # 21, p. 8283 - 8286]
[34]Current Patent Assignee: SHENYANG PHARMACEUTICAL UNIVERSITY - CN105541828, 2016, A Location in patent: Paragraph 0445; 0450; 0451
[35]Location in patent: experimental part Janssen, Michiel H. A.; Chesa Castellana, Juan F.; Jackman, Hayley; Dunn, Peter J.; Sheldon, Roger A. [Green Chemistry, 2011, vol. 13, # 4, p. 905 - 912]
[36]Luly, Jay R.; Dellaria, Joseph F.; Plattner, Jacob J.; Soderquist, Jeffrey L.; Yi, Nwe [Journal of Organic Chemistry, 1987, vol. 52, # 8, p. 1487 - 1492] Konradi, Andrei W.; Kemp, Scott J.; Pedersen, Steven F. [Journal of the American Chemical Society, 1994, vol. 116, # 4, p. 1316 - 1323]
[37]Fournie-Zaluski; Coric; Turcaud; Bruetschy; Lucas; Noble; Roques [Journal of Medicinal Chemistry, 1992, vol. 35, # 7, p. 1259 - 1266]
[38]Caputo, Romualdo; Cassano, Ersilia; Longobardo, Luigi; Palumbo, Giovanni [Tetrahedron Letters, 1995, vol. 36, # 1, p. 167 - 168]
[39]Sajiki, Hironao; Ong, Karen Y. [Tetrahedron, 1996, vol. 52, # 46, p. 14507 - 14514]
[40]Toujas, Jean-Louis; Jost, Eric; Vaultier, Michel [Bulletin de la Societe Chimique de France, 1997, vol. 134, # 7, p. 713 - 718]
[41]Sutton, Peter W.; Bradley, Adrian; Elsegood, Mark R. J.; Farras, Jaume; Jackson, Richard F. W.; Romea, Pedro; Urpi, Felix; Vilarrasa, Jaume [Tetrahedron Letters, 1999, vol. 40, # 13, p. 2629 - 2632]
[42]Veeresa [Synthetic Communications, 2000, vol. 30, # 8, p. 1479 - 1487]
[43]Braga, Antonio L.; Paixao, Marcio W.; Luedtke, Diogo S.; Silveira, Claudio C.; Rodrigues, Oscar E. D. [Organic Letters, 2003, vol. 5, # 15, p. 2635 - 2638] Braga, Antonio L.; Paixão, Márcio W.; Marin, Graciane [Synlett, 2005, # 11, p. 1675 - 1678]
[44]Kotoku, Naoyuki; Cao, Liwei; Aoki, Shunji; Kobayashi, Motomasa [Heterocycles, 2005, vol. 65, # 3, p. 563 - 578]
[45]Datta, Apurba; Veeresa, Gududuru [Journal of Organic Chemistry, 2000, vol. 65, # 22, p. 7609 - 7611]
[46]Talluri, Siva Kumar; Sudalai, Arumugam [Tetrahedron, 2007, vol. 63, # 39, p. 9758 - 9763]
[47]Current Patent Assignee: SANTEN PHARMACEUTICAL CO LTD - US6410576, 2002, B1
[48]Current Patent Assignee: MERCK & CO INC - US5472978, 1995, A
[49]Current Patent Assignee: PFIZER INC - US4882420, 1989, A
[50]Location in patent: experimental part Virlouvet, Mickael; Goesmann, Helmut; Feldmann, Claus; Podlech, Joachim [Monatshefte fur Chemie, 2010, vol. 141, # 2, p. 177 - 198]
[51]Location in patent: body text Mohapatra, Debendra K.; Maity, Pradip K.; Ghorpade, Ravindra V.; Gurjar, Mukund K. [Heterocycles, 2009, vol. 77, # 2, p. 865 - 872]
[52]Location in patent: experimental part Bellingham, Richard; Buswell, A. Mark; Choudary, Bernie M.; Gordon, Andrew H.; Moore, Steve O.; Peterson, Matthew; Sasse, Mike; Shamji, Amin; Urquhart, Michael W. J. [Organic Process Research and Development, 2010, vol. 14, # 5, p. 1254 - 1263]
[53]Location in patent: scheme or table Hunt, Thomas; Atherton-Watson, Hazel C.; Collingwood, Stephen P.; Coote, Kevin J.; Czarnecki, Sarah; Danahay, Henry; Howsham, Catherine; Hunt, Peter; Paisley, Derek; Young, Alice [Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 8, p. 2877 - 2879]
[54]Shi, Zugui; Yu, Peiyuan; Loh, Teck-Peng; Zhong, Guofu [Angewandte Chemie - International Edition, 2012, vol. 51, # 31, p. 7825 - 7829]
[55]Reddy Guduru, Shiva Krishna; Chamakuri, Srinivas; Chandrasekar, Gayathri; Kitambi, Satish Srinivas; Arya, Prabhat [ACS Medicinal Chemistry Letters, 2013, vol. 4, # 7, p. 666 - 670]
[56]Gooding, Owen W.; Lindberg, Thomas; Miller, Wendy; Munyak, Edward; Vo, Lanchi [Organic Process Research and Development, 2001, vol. 5, # 3, p. 283 - 293]
[57]Jogula, Srinivas; Dasari, Bhanudas; Khatravath, Mahender; Chandrasekar, Gayathri; Kitambi, Satish Srinivas; Arya, Prabhat [European Journal of Organic Chemistry, 2013, # 23, p. 5036 - 5040]
[58]Sonnenberg, Jessica F.; Lough, Alan J.; Morris, Robert H. [Organometallics, 2014, vol. 33, # 22, p. 6452 - 6465]
[59]Hou, Wenduan; Wei, Qi; Liu, Guisheng; Chen, Jing; Guo, Jing; Peng, Yungui [Organic Letters, 2015, vol. 17, # 19, p. 4870 - 4873]
[60]Kim, Ho Shin; Jin, Mi-Kyoung; Kang, Sang-Uk; Lim, Ju-Ok; Tran, Phuong-Thao; Hoang, Van-Hai; Ann, Jihyae; Ha, Tae-Hwan; Pearce, Larry V.; Pavlyukovets, Vladimir A.; Blumberg, Peter M.; Lee, Jeewoo [Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 12, p. 2685 - 2688]
[61]Cui, Zhihao; Du, Da-Ming [Organic Letters, 2016, vol. 18, # 21, p. 5616 - 5619]
[62]K'tir, Hacène; Aouf, Zineb; Souk, Tan Otea; Zerrouki, Rachida; Berredjem, Malika; Aouf, Nour-Eddine [Phosphorus, Sulfur and Silicon and the Related Elements, 2017, vol. 192, # 5, p. 555 - 559]
[63]Sukhanova, Anna A.; Puchkin, Ilya A.; Vasil'ev, Andrei A.; Zlotin, Sergei G. [Tetrahedron Asymmetry, 2017, vol. 28, # 12, p. 1834 - 1841]
[64]Xu, Xiaoying; Zhang, Kaifan; Li, Panpan; Yao, Hequan; Lin, Aijun [Organic Letters, 2018, vol. 20, # 7, p. 1781 - 1784]
[65]Kaźmierczak, Marcin; Kubicki, Maciej; Koroniak, Henryk [European Journal of Organic Chemistry, 2018, vol. 2018, # 27, p. 3844 - 3852]
[66]Zhao, Liyu; Tian, Linfeng; Sun, Nannan; Sun, Yin; Chen, Yixuan; Wang, Xinran; Zhao, Shizhen; Su, Xin; Zhao, Dongmei; Cheng, Maosheng [European Journal of Medicinal Chemistry, 2019, vol. 177, p. 374 - 385]
[67]Wang, Kaiye; Xiang, Yanan; Shi, Zhujun; Wang, Hongyu; Li, Na; Tang, Bo [Organic and Biomolecular Chemistry, 2019, vol. 17, # 26, p. 6351 - 6354]
[68]Pirola, Margherita; Puglisi, Alessandra; Raimondi, Laura; Forni, Alessandra; Benaglia, Maurizio [Molecules, 2019, vol. 24, # 12]
[69]Chen, Jianzhong; Gridnev, Ilya D.; Hu, Yawen; Li, Bowen; Zhang, Wanbin; Zhang, Zhenfeng [Angewandte Chemie - International Edition, 2020, vol. 59, # 13, p. 5371 - 5375][Angew. Chem., 2020, vol. 132, # 13, p. 5409 - 5413,5]
[70]Ajayi, Oluwatomi; Collins, Jasmine; Crown, Olamide; Nyamwihura, Rogers; Ogungbe, Ifedayo Victor; Zhang, Huaisheng [Bioorganic and medicinal chemistry letters, 2020, vol. 30, # 14]
[71]Garbacz, Mateusz; Stecko, Sebastian [Advanced Synthesis and Catalysis, 2020, vol. 362, # 15, p. 3213 - 3222]
[72]Zhang, Huaisheng; Harmon, Moeshia; Radoshitzky, Sheli R.; Soloveva, Veronica; Kane, Christopher D.; Duplantier, Allen J.; Ogungbe, Ifedayo Victor [ACS Medicinal Chemistry Letters, 2020, vol. 11, # 11, p. 2139 - 2145]
[73]An, Yunfei; Fan, Haiyan; Han, Jun; Liu, Wenxia; Sun, Bin; Xie, Honglei [European Journal of Medicinal Chemistry, 2022, vol. 227]

4
[ 88463-18-7 ]
[ 4248-19-5 ]
[ 102-93-2 ]
[ 66605-57-0 ]

Reference： [1]Journal of the Chemical Society. Chemical communications,1982,p. 639 - 640

5
[ 51987-73-6 ]
[ 66605-57-0 ]

Yield	Reaction Conditions	Operation in experiment
100%	With sodium tetrahydroborate In tetrahydrofuran; methanol at 65℃; for 1h;
100%	With sodium tetrahydroborate; calcium chloride In methanol at 20℃; for 20h;	N-(tert-Butyloxycarbonyl)-L-phenylalaninol (2)2 A solution of methyl ester (4 g, 14.24 mmol) and CaCl2 (6.33 g, 57 mmol) in MeOH (200 mL)was treated in portions with NaBH4 (2.18 g, 57 mmol) and further stirred at room temperature 20h. The solvent was removed under reduced pressure and the residue was acidified with 5% HCl.The precipitate was filtered off and dried to obtain pure N-(tert-butyloxycarbonyl)-Lphenylalaninol2 (3.72 g, 100%), as a white foam. Rf 0.21 (n-hexane/EtOAc; 3/1). 1H NMR (500MHz, CDCl3) δ: 7.31-7.28 (m, 2H), 7.26-7.2 (m, 3H), 4.78 (brs, 1H), 3.86 (brs, 1H), 3.65 (dd, J =3.0 Hz, 11.0 Hz, 1H), 3.54 (dd, J = 3.0 Hz, 11.0 Hz, 1H), 2.83 (d, J = 7.0 Hz, 2H), 1.41 (s, 9H).
94%	With sodium tetrahydroborate; lithium chloride In tetrahydrofuran at 20℃; Inert atmosphere;

94%	With methanol; sodium tetrahydroborate; lithium chloride at 5 - 20℃; Inert atmosphere;	4 Synthesis of compound 7b Compound 8b (27.9 g, 0. eq.) and lithium chloride (8.5 g, 2.0 eq.) were added to methanol (500 ml) and dissolved with stirring under nitrogen. The mixture was cooled to below 5 ° C in an ice-water bath, sodium borohydride (7.5g, 2. Oeq.) was added in portions to the reaction solution, and the reaction mixture was incubated at room temperature. The reaction was monitored by TLC until the starting material disappeared. The reaction was placed in ice water The bath was cooled to below 5 ° C, 15 ml of water was added dropwise to the mixture, and 2N hydrochloric acid was added dropwise to a pH of 2-3. The majority of the solvent was evaporated off and the residue was adjusted to pH 9 with 2 mol / L NaOH solution. The aqueous layer was extracted with dichloromethane (30 ml x 3) and the combined organic layers were washed with water (30 ml) and saturated brine (30 ml) Sodium drying. Filtration and concentration of the filtrate under reduced pressure gave a crude yellow oil. The crude product was recrystallized from ethyl acetate n-heptane (2: 1 mixed solvent) to give compound 7b (23.6 g, yield 94%).
90%	With sodium tetrahydroborate; acetic acid In 1,4-dioxane at 80℃;
90%	With lithium aluminium tetrahydride In tetrahydrofuran at 0℃; for 1h;
89%	With lithium borohydride In 1,2-dimethoxyethane
89%	With sodium tetrahydroborate; lithium chloride In tetrahydrofuran; ethanol at 20℃; for 12h;
85%	With sodium tetrahydroborate; ethanol; cerium(III) chloride heptahydrate at 20℃; for 24h; chemospecific reaction;
82%	With sodium tetrahydroborate; ethanol; lithium chloride In tetrahydrofuran at 0 - 20℃; for 12h;
82%	With sodium tetrahydroborate; lithium chloride In tetrahydrofuran; ethanol at 20℃; for 16h;
81%	Stage #1: (S)-2-tert-butoxycarbonylamino-3-phenyl-propionic acid methyl ester With triethyl borane; sodium methylate In tetrahydrofuran; diethyl ether at 20℃; for 10h; Inert atmosphere; Stage #2: With sodium hydroxide In methanol; diethyl ether; toluene at 20℃; for 2h;
72%	With sodium tetrahydroborate; lithium iodide In 1,2-dimethoxyethane at 40℃; for 2.5h;
70%	With diisobutylaluminum hydride In hexane; toluene
	With lithium borohydride In ethanol Yield given;
	With lithium borohydride In tetrahydrofuran; ethanol
	With sodium tetrahydroborate; lithium chloride In tetrahydrofuran; ethanol
	With sodium tetrahydroborate; calcium chloride In tetrahydrofuran; ethanol at 0℃; for 5h;
	With sodium tetrahydroborate In ethanol at 0℃; for 24.1667h; Inert atmosphere; Reflux;
	With lithium aluminium tetrahydride In tetrahydrofuran at 0 - 25℃; for 4h;	3.5.3. General method for preparation of compounds (5) General procedure: To a dried methanol (50 mL) solution of 4 (3.3 g, 20 mmol), thionyl chloride (3.57 g, 30 mmol) was slowly added over 30 minat 0 °C, and then, the solution was maintained at room temperature for 18 h. The solvent was evaporated to obtain a solid in quantitative yield, which was dissolved in dichloromethane (120 mL), and triethylamine (12.1 g, 120 mL) and di-tert-butyldicarbonate (9.6 g, 40 mmol) were added to the dichloromethane solution. The reaction mixture was stirred at 25 °C for 24 h. Afterc ompletion of the reaction, the solution was washed with phosphoric acid (50 x 3 mL), saturated sodium bicarbonate (50 x 3 mL) and saturated sodium chloride (50 x 3 mL), dried over anhydrous sodium sulfate, filtered and evaporated under reduced pressure to afford a solid to which lithium aluminum hydride (13 mmol) in the presence of dried tetrahydrofuran (25 mL) was added at 0 °C. The reaction mixture was maintained at room temperature for 4 h, and then water was added until the lithium aluminum hydride reacted completely. Next, the solution was filtered, and the residue was washed with tetrahydrofuran (20 x 2 mL).The combined organic solvent phase was evaporated under reduced pressure to yield the crude product, which was purified using column chromatography (petroleum ether/acetone) to afford 5a-5g.
	With lithium aluminium tetrahydride at 0℃;
	With lithium aluminium tetrahydride In tetrahydrofuran at 0 - 20℃; for 1h;
	With lithium aluminium tetrahydride In tetrahydrofuran at 20℃; for 18h;
	With sodium tetrahydroborate
	With lithium aluminium tetrahydride In tetrahydrofuran at 0 - 20℃; for 12h; Inert atmosphere;

Reference： [1]Kondaparla, Srinivasarao; Soni, Awakash; Manhas, Ashan; Srivastava, Kumkum; Puri, Sunil K.; Katti [RSC Advances, 2016, vol. 6, # 107, p. 105676 - 105689]
[2]Le, Hai Van; Tran, Loc Van; Tran, Anh Tuan; Tran, Thao Thi Phuong; Tran, Sung Van; Tran, Chien Van [Synlett, 2022, vol. 33, # 2, p. 187 - 195]
[3]Location in patent: experimental part Spaeth, Andreas; Gonschor, Janina; Koenig, Burkhard [Monatshefte fur Chemie, 2011, vol. 142, # 12, p. 1289 - 1308]
[4]Current Patent Assignee: ZHEJIANG YONGNING PHARMA - CN105198829, 2017, B Location in patent: Paragraph 0073-0075
[5]Soucek, Milan; Urban, Jan; Saman, David [Collection of Czechoslovak Chemical Communications, 1990, vol. 55, # 3, p. 761 - 765]
[6]Seo, Woo Duck; Curtis-Long, Marcus J.; Kim, Jin Hyo; Park, Jong Keun; Park, Ki Min; Park, Ki Hun [Synlett, 2005, # 15, p. 2289 - 2292]
[7]Van den Broek; Fennis; Arevalo; Lazaro; Ballesta; Lelieveld; Ottenheijm [European Journal of Medicinal Chemistry, 1989, vol. 24, # 5, p. 503 - 510]
[8]Shie, Jiun-Jie; Fang, Jim-Min; Kuo, Tun-Hsun; Kuo, Chih-Jung; Liang, Po-Huang; Huang, Hung-Jyun; Wu, Yin-Ta; Jan, Jia-Tsrong; Cheng, Yih-Shyun E.; Wong, Chi-Huey [Bioorganic and Medicinal Chemistry, 2005, vol. 13, # 17, p. 5240 - 5252]
[9]Location in patent: experimental part Xu, Yinan; Wei, Yunyang [Synthetic Communications, 2010, vol. 40, # 22, p. 3423 - 3429]
[10]Shashidhar Kumar; Haritha; Venkateswara Rao [Tetrahedron Letters, 2003, vol. 44, # 22, p. 4261 - 4263]
[11]Location in patent: scheme or table Ramu, Errabelli; Venkateswara Rao [Tetrahedron Asymmetry, 2009, vol. 20, # 19, p. 2201 - 2204]
[12]Peng, Dongjie; Zhang, Mintao; Huang, Zheng [Chemistry - A European Journal, 2015, vol. 21, # 42, p. 14737 - 14741]
[13]Brouwer, Arwin J.; Mulders, Suzanne J. E.; Liskamp, Rob M. J. [European Journal of Organic Chemistry, 2001, # 10, p. 1903 - 1915]
[14]Miles, Nicholas J.; Sammes, Peter G.; Kennewell, Peter D.; Westwood, Robert [Journal of the Chemical Society. Perkin transactions I, 1985, p. 2299 - 2306]
[15]Higashiura, Kunihiko; Morino, Hiroe; Matsuura, Hirohide; Toyomaki, Yoshio; Ienaga, Kazuharu [Journal of the Chemical Society. Perkin transactions I, 1989, p. 1479 - 1481]
[16]Wyslouch, Aleksandra; Lisowski, Marek; Siemion, Ignacy Z. [Bulletin of the Polish Academy of Sciences: Chemistry, 1994, vol. 42, # 1, p. 117 - 130]
[17]Zygmunt, Jan; Gancarz, Roman; Lejczak, Barbara; Wieczorek, Piotr; Kafarski, Pawel [Bioorganic and Medicinal Chemistry Letters, 1996, vol. 6, # 24, p. 2989 - 2992]
[18]Fu, Yiqiu; Xu, Bo; Zou, Xiaomin; Ma, Chao; Yang, Xiaoming; Mou, Ke; Fu, Gang; Lue, Yang; Xu, Ping [Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 4, p. 1102 - 1106]
[19]Adams, Harry; Collins, Rebecca C.; Jones, Simon; Warner, Christopher J. A. [Organic Letters, 2011, vol. 13, # 24, p. 6576 - 6579]
[20]Yang, Dezhi; Wang, Peng; Liu, Jianzhen; Xing, Hualu; Liu, Yang; Xie, Wencheng; Zhao, Guisen [Bioorganic and Medicinal Chemistry, 2014, vol. 22, # 1, p. 366 - 373]
[21]Liu, Hongtao; Xu, Lianhong; Hui, Hon; Vivian, Randy; Callebaut, Christian; Murray, Bernard P.; Hong, Allen; Lee, Melody S.; Tsai, Luong K.; Chau, Jennifer K.; Stray, Kirsten M.; Cannizzaro, Carina; Choi, You-Chul; Rhodes, Gerry R.; Desai, Manoj C. [Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 3, p. 989 - 994]
[22]Bera, Saurav; Panda, Gautam [Organic and Biomolecular Chemistry, 2014, vol. 12, # 23, p. 3976 - 3985]
[23]Debia, Natalí P.; Saraiva, Maiara T.; Martins, Bruna S.; Beal, Roiney; Gonçalves, Paulo F. B.; Rodembusch, Fabiano S.; Alves, Diego; Lüdtke, Diogo S. [Journal of Organic Chemistry, 2018, vol. 83, # 3, p. 1348 - 1357]
[24]Kondaparla, Srinivasarao; Debnath, Utsab; Dola, Vasantha Rao; Sinha, Manish; Katti, Seturam B.; Soni, Awakash; Srivastava, Kumkum; Puri, Sunil K. [Antimicrobial Agents and Chemotherapy, 2018, vol. 62, # 12]
[25]Debia, Natalí P.; Rodríguez, Juan J.P.; da Silveira, Carolina H.; Chaves, Otavio A.; Iglesias, Bernardo A.; Rodembusch, Fabiano S.; Lüdtke, Diogo S. [Journal of Molecular Liquids, 2020, vol. 309]

6
[ 66605-57-0 ]
[ 72155-45-4 ]

Yield	Reaction Conditions	Operation in experiment
100%	With Dess-Martin periodane In dichloromethane at 20℃; for 2.67h;	1.h h) Preparation of 1-h: 29.7 g (70.0 mmol) Dess-Martin-periodinane were suspended in 150 ml dichloromethane, then within 40 minutes a solution of 16.0 g (63.7 mmol) Boc-phenylalaminol in 150 ml dichloromethane was metered in. The reaction solution was stirred for 2 hours at ambient temperature, then combined with 200 ml 20% KHCO3 solution and 200 ml 10% Na2S2O3 solution. The mixture was stirred for 20 min at ambient temperature, the phases were separated and the organic phase was washed with 20% KHCO3 solution and water. The organic phase was dried and evaporated to dryness using the rotary evaporator. This gave a quantitative yield of 1-h as white crystals.
100%	With oxalyl dichloride; dimethyl sulfoxide; triethylamine In dichloromethane at -78 - 20℃; Inert atmosphere;
100%	Stage #1: (S)-N-tert-butoxycarbonyl-2-amino-3-phenylpropanol With Dess-Martin periodane In dichloromethane at 20℃; for 2h; Stage #2: With potassium hydrogencarbonate; sodium thiosulfate In dichloromethane at 20℃; for 0.333333h;	7.g 29.7 g (70.0 mmol) Dess-Martin-periodinane were suspended in 150 ml dichloromethane, then within 40 minutes a solution of 16.0 g (63.7 mmol) Boc-phenylalaninol in 150 ml dichloromethane was metered in. The reaction solution was stirred for 2 hours at ambient temperature, then combined with 200 ml 20% KHCO3 solution and 200 ml 10% Na2S2O3 solution. The mixture was stirred for 20 min at ambient temperature, the phases were separated and the organic phase was washed with 20% KHCO3 solution and water. The organic phase was dried and evaporated to dryness using the rotary evaporator. This gave a quantitative yield of 7-g as white crystals.

100%	With Dess-Martin periodane In dichloromethane at 20℃; for 2.66667h;	1.j 29.7 g (70.0 mmol) of Dess-Martin periodinane were suspended in 150 ml dichloromethane, then within 40 minutes a solution of 16.0 g (63.7 mmol) Boc-phenyl-alaninol in 150 ml dichloromethane was metered in. The reaction solution was stirred for 2 hours at ambient temperature, then combined with 200 ml 20% KHCO3 solution and 200 ml 10% Na2S2O3 solution. The mixture was stirred for 20 min at ambient temperature, the phases were separated and the organic phase was washed with 20% KHCO3 solution and water. The organic phase was dried and evaporated to dryness using the rotary evaporator. Quantitative yield of 1-j as white crystals.
100%	Stage #1: (S)-N-tert-butoxycarbonyl-2-amino-3-phenylpropanol With oxalyl dichloride; dimethyl sulfoxide In dichloromethane at -78℃; Stage #2: With triethylamine In dichloromethane at -78 - 20℃; Stage #3: With sodium hydrogencarbonate In dichloromethane	1.c (c) 1 ,1-Dimethylethyl [(1S)-1-formyl-2-phenylethyl]carbamate. To a solution of oxalyl chloride (1.59 ml_, 18.14 mmol) in dichloromethane (60 ml.) at -78° C was slowly added dimethyl sulfoxide (2.58 ml_, 36.3 mmol). The mixture was stirred for 10 minutes before slowly adding a solution of 1 ,1-dimethylethyl [(1 S)-2-hydroxy-1- (phenylmethyl)ethyl]carbamate (3.04 g, 12.10 mmol) in dichloromethane (20 ml_). The mixture was stirred for 20 minutes before slowly adding triethylamine (5.06 ml_, 36.3 mmol) and the mixture was stirred for 30 minutes at -78° C and then warmed to ambient temperature for 30 minutes. Saturated sodium bicarbonate and brine were added and the mixture was diluted with dichloromethane. The organic phase was washed with saturated sodium bicarbonate, then brine, dried over magnesium sulfate, filtered and concentrated to give the title compound as a white solid (3.02 g, 100%). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.44 (s, 9 H), 3.13 (d, J=6.6 Hz, 2 H), 4.33 - 4.54 (m, 1 H), 4.97 - 5.12 (m, 1 H), 7.14 - 7.22 (m, 2 H), 7.24 - 7.37 (m, 3 H), 9.64 (s, 1 H).
99%	With sulfur trioxide pyridine complex; dimethyl sulfoxide; triethylamine In dichloromethane at -10℃;
99%	With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; bisacetoxybromate(I) resin In dichloromethane at 20℃; for 2h;
98%	With sodium hypochlorite; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; sodium hydrogencarbonate; potassium bromide In dichloromethane at -5℃; for 0.5h;
98%	With sodium hydrogencarbonate; Dess-Martin periodane In dichloromethane for 2h;
97%	With 1-hydroxy-3H-benz[d][1,2]iodoxole-1,3-dione In ethyl acetate Heating;
96%	With oxalyl dichloride; thioacetone at -63℃;
96%	With Dess-Martin periodane In dichloromethane at 20℃; for 1h; Inert atmosphere;
95%	With pyridine; sulfur trioxide; dimethyl sulfoxide; triethylamine In dichloromethane at 0℃; for 1h;
94.2%	With pyridine-SO₃ complex; triethylamine In dimethyl sulfoxide at 10 - 15℃; for 1.5h;
93%	With 1-hydroxy-3H-benz[d][1,2]iodoxole-1,3-dione In dimethyl sulfoxide at 20℃; for 15h;
93%	With sodium hypochlorite solution; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; sodium hydrogencarbonate; sodium bromide In dichloromethane; water at 5℃;	8 Synthesis of compound 6b To a 500 ml three necked flask was added compound 7b (25.1 g, 1.0eq), sodium bicarbonate (12.6 g, 1.5 eq.), Sodium bromide (10.3 g, 1.0 eq.), TEMPO , 0. leq.), Dichloromethane (300 ml) and water (100 ml). After adding, the reaction solution was cooled to below 5 ° C. To the reaction mixture was added dropwise sodium hypochlorite solution (75ml, l.leq.), controlled should be fluid temperature is not higher than 5 ° C. The addition is complete, the reaction mixture was stirred until the raw material consumption is completed. A 10% sodium bisulfite solution (115 ml) was added dropwise to the reaction solution to control the internal temperature not to exceed 15 ° C. The mixture was stirred for 15 minutes and allowed to stand for separation. The aqueous layer was extracted with dichloromethane (50 ml × 2). The combined organic layers were washed with saturated brine and dried over anhydrous sodium sulfate. Filtered and the filtrate evaporated under reduced pressure to give compound 6b (23. lg, 93% yield).
93%	With Dess-Martin periodane In 1,4-dioxane; dichloromethane at 25℃; for 0.666667h;
91%	With Dess-Martin periodane; <i>tert</i>-butyl alcohol In dichloromethane Ambient temperature;
86%	With Dess-Martin periodane In dichloromethane for 6h; Inert atmosphere;
85%	Stage #1: (S)-N-tert-butoxycarbonyl-2-amino-3-phenylpropanol With Dess-Martin periodane In dichloromethane at 20℃; for 14.25h; Stage #2: With sodium hydrogencarbonate; sodium thiosulfate In dichloromethane	1 11.4 g (26.9 mmol) of Dess-Martin periodinane were suspended in 75 ml dichloromethane and a solution of 6.08 g (24.2 mmol) (S)-(-)-2-(tert-butoxycarbonylamino)-3-phenyl-1-propanol and 25 ml dichloromethane was added dropwise to the existing suspension within 15 min at ambient temperature and then stirred for 14 h at ambient temperature. Then Na2S2O3 solution (10%) and saturated NaHCO3 were added dropwise and the mixture was stirred for 30 min at ambient temperature. The phases were separated, the inorganic phase was extracted with dichloromethane, the combined organic phases were washed with saturated NaHCO3 solution, dried and evaporated down in vacuo. The crude product was used in the next test without any further purification.Yield: 6.0 g (20.5 mmol) (85%) 1-a.ES-MS (M+)=249
84%	With sodium hypochlorite; 4-acetylamino-2,2,6,6-tetramethyl-1-piperidinoxy; sodium bromide In ethyl acetate at 0℃; for 2h;
82%	With 2,2,6,6-tetramethyl-piperidine-N-oxyl; sodium hypochlorite; tetrabutylammomium bromide; sodium hydrogencarbonate In toluene at 0℃; for 0.0238889h;
82%	With DMP In dichloromethane at 0 - 20℃;
81%	With sodium hydrogencarbonate; Dess-Martin periodane In dichloromethane at 0 - 20℃; for 5.16h;	tert-Butyl (S)-(1-oxo-3-phenylpropan-2-yl)carbamate (S6) tert-Butyl (S)-(1-hydroxy-3-phenylpropan-2-yl)carbamate (S5) (377 mg, 1.5 mmol, 1.0 equiv) was dissolved in dichloromethane (13 mL) and cooled to 0 °C. Sodium bicarbonate (2.52 g, 30.0 mmol, 20 equiv) and freshly prepared Dess-Martin periodinane (700 mg, 1.65 mmol, 1.1 equiv) were added sequentially. The mixture was stirred at 0 °C for 10 min before the ice bath was removed. The mixture was stirred at ambient temperature for 5 h. Diethyl ether (15 mL) was added and a saturated aqueous solution of sodium sulphate and sodium bicarb (10 mL) was added slowly. The mixture was extracted with dichloromethane (3 × 30 mL). The combined organic phases were dried over MgSO4 and the solvent was removed in vacuo. The residue was purified by column chromatography (cyclohexane : ethyl acetate, 4:1) and the product (304 mg, 1.2 mmol, 81%) was obtained as a white solid.
80%	With dipyridinium dichromate In dichloromethane Ambient temperature;
80%	With 2,2,6,6-tetramethyl-piperidine-N-oxyl; sodium hypochlorite solution; sodium hydrogencarbonate; sodium bromide In water; ethyl acetate; toluene at 0℃;
77%	With pyridine-SO₃ complex; N-ethyl-N,N-diisopropylamine In dichloromethane; dimethyl sulfoxide for 1h; cooling;
77%	With sulfur trioxide pyridine complex; N-ethyl-N,N-diisopropylamine In dichloromethane; dimethyl sulfoxide at 0℃; for 1h;	8.2 (2) N- (tert-Butoxycarbonyl)-L-phenylalaninol (69 g, 0.28 mol) was dissolved in DMSO (280 mL) and CH2Cl2 (140 mL), and the solution was in an ice-bath. N, N- diisopropylethylamine (106 g, 0.82 mol) and a suspension of purified sulfur trioxide pyridine complex (130 g, 0.82 mol) in DMSO (100 mL) were added thereto. The mixture was stirred for 1 hour under the same condition. The reaction mixture was diluted with EtOAc (1.5 L), and the solution was washed with 1M HC1, saturated aqueous NaHC03 and saturated aqueous NaCl, dried over anhydrous MgS04, and concentrated in vacuo. The residue was crystallized from a mixture of hexane and EtOAc to give N- (tert-butoxycarbonyl)-L-phenylalaninal (53 g, 77%) as colorless crystals.
77%	With N-ethyl-N,N-diisopropylamine In hexane; dichloromethane; dimethyl sulfoxide; ethyl acetate	R.8.2 (3S)-3-Amino-N-ethyl-2-hydroxy-4-phenylbutanamide hydrochloride (2) N-(tert-Butoxycarbonyl)-L-phenylalaninol (69 g, 0.28 mol) was dissolved in DMSO (280 mL) and dichloromethane (140 mL), and this solution was cooled in an ice bath. Then, N,N-diisopropylethylamine (110 g, 0.82 mol) and a suspension of purified sulfur trioxide pyridine complex (130 g, 0.82 mol) in DMSO (100 mL) were added thereto. This solution was stirred for 1 hour under ice-cold conditions. The reaction solution was diluted with ethyl acetate (1.5 L), washed with 1M hydrochloric acid, saturated aqueous sodium hydrogen carbonate solution, and saturated saline solution, dehydrated with anhydrous magnesium sulfate, and concentrated in vacuo. The residue was crystallized from a liquid mixture of ethyl acetate/hexane mixture, thereby yielding N-(tert-butoxycarbonyl)-L-phenylalaninal (53 g, 77%) as a colorless crystal.
77%	With sulfur trioxide pyridine complex; N-ethyl-N,N-diisopropylamine In dichloromethane; dimethyl sulfoxide for 1h; Cooling with ice;	8.2 (2) N-(tert-l3utoxycarbonyl)-E-phenylalaninol (69 g, 0.28 mol) was dissolved in DMSO (280 mE) and dichloromethane(140 mE), and this solution was cooled in an ice bath. Then, N,N-diisopropylethylamine (110 g, 0.82 mol) and a suspension of purified sulfur trioxide pyridine complex (130 g, 0.82 mol) in DMSO (100 mE) were added thereto. This solution was stirred for 1 hour under ice-cold conditions. The reactionsolution was diluted with ethyl acetate (1.5 E), washed with1 M hydrochloric acid, saturated aqueous sodium hydrogen carbonate solution, and saturated saline solution, dehydrated with anhydrous magnesium sulfate, and concentrated in vacuo. The residue was crystallized from a liquid mixture ofethyl acetate/hexane mixture, thereby yielding N-(tert-butoxycarbonyl)-E-phenylalaninal (53 g, 77%) as a colorlesscrystal.
77%	With sulfur trioxide pyridine complex; N-ethyl-N,N-diisopropylamine In dichloromethane; dimethyl sulfoxide for 1h; Cooling with ice;	R.8.2 (3S)-3-Amino-N-ethyl-2-hydroxy-4-phenylbutanamide hydrochloride (2) N-(tert-Butoxycarbonyl)-L-phenylalaninol (69 g, 0.28 mol) was dissolved in DMSO (280 mL) and dichloromethane (140 mL), and this solution was cooled in an ice bath. Then, N,N-diisopropylethylamine (110 g, 0.82 mol) and a suspension of purified sulfur trioxide pyridine complex (130 g, 0.82 mol) in DMSO (100 mL) were added thereto. This solution was stirred for 1 hour under ice-cold conditions. The reaction solution was diluted with ethyl acetate (1.5 L), washed with 1M hydrochloric acid, saturated aqueous sodium hydrogen carbonate solution, and saturated saline solution, dehydrated with anhydrous magnesium sulfate, and concentrated in vacuo. The residue was crystallized from a liquid mixture of ethyl acetate/hexane mixture, thereby yielding N-(tert-butoxycarbonyl)-L-phenylalaninal (53 g, 77%) as a colorless crystal.
75%	With sulfur trioxide pyridine complex; dimethyl sulfoxide; triethylamine In dichloromethane at 0℃;
64%	With 1-butyl-3-methylimidazolium chloride; 1-hydroxy-3H-benz[d][1,2]iodoxole-1,3-dione at 20℃; for 4h;
52%	With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; [bis(acetoxy)iodo]benzene In dichloromethane at 35℃; for 0.075h; Flow reactor; chemoselective reaction;
51%	With 1-hydroxy-3H-benz[d][1,2]iodoxole-1,3-dione In acetonitrile for 0.5h; Reflux;
	With sulfur trioxide pyridine complex; triethylamine In dimethyl sulfoxide; benzene at 20 - 25℃; for 0.333333h;
	at -60℃; Swern oxidation;
	With pyridine; sulfur trioxide; triethylamine 1) DMSO, 2) CH₂Cl₂; Yield given. Multistep reaction;
	With pyridine-SO₃ complex
	With oxalyl dichloride; triethylamine In dichloromethane at -78℃;
	With pyridine-SO₃ complex; triethylamine In dichloromethane; dimethyl sulfoxide for 0.166667h; Ambient temperature; Yield given;
	With dimethyl sulfoxide; triethylamine 1.) CH₂Cl₂, -63 deg C, 20 min, 2.) CH₂Cl₂, -63 deg C, 20 min; Multistep reaction;
6.32 g	With oxalyl dichloride; triethylamine In dichloromethane; dimethyl sulfoxide at -55℃; for 1h;
	With pyridine-SO₃ complex; TEA In dichloromethane; dimethyl sulfoxide for 0.166667h; Ambient temperature;
	With 4-methyl-morpholine; oxalyl dichloride; dimethyl sulfoxide In dichloromethane at -65 - 0℃;
	With oxalyl dichloride; dimethyl sulfoxide; triethylamine 1.) CH₂Cl₂, -78 deg C, 15 min, 2.) -78 deg C, 25 min; Yield given. Multistep reaction;
	With sulfur trioxide In pyridine; dimethyl sulfoxide; triethylamine for 0.333333h; Ambient temperature;
	With oxalyl dichloride; dimethyl sulfoxide; triethylamine In dichloromethane at -63℃; Yield given;
	With oxalyl dichloride; dimethyl sulfoxide; N-ethyl-N,N-diisopropylamine In hexane; chloroform at -78 - 0℃; for 1.5h;
	With Dess-Martin periodane In dichloromethane at 25℃; for 2h;

Reference： [1]Current Patent Assignee: C.H. Boehringer Sohn AG & Co. KG - US2009/42867, 2009, A1 Location in patent: Page/Page column 33
[2]Flentge, Charles A.; Randolph, John T.; Huang, Peggy P.; Klein, Larry L.; Marsh, Kennan C.; Harlan, John E.; Kempf, Dale J. [Bioorganic and Medicinal Chemistry Letters, 2009, vol. 19, # 18, p. 5444 - 5448]
[3]Current Patent Assignee: C.H. Boehringer Sohn AG & Co. KG - US2010/144681, 2010, A1 Location in patent: Page/Page column 83
[4]Current Patent Assignee: C.H. Boehringer Sohn AG & Co. KG - US2006/223759, 2006, A1 Location in patent: Page/Page column 143
[5]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2011/17395, 2011, A1 Location in patent: Page/Page column 44
[6]Catalano, John G; Deaton, David N; Furfine, Eric S; Hassell, Annie M; McFadyen, Robert B; Miller, Aaron B; Miller, Larry R; Shewchuk, Lisa M; Willard Jr., Derril H; Wright, Lois L [Bioorganic and medicinal chemistry letters, 2004, vol. 14, # 1, p. 275 - 278]
[7]Bruenjes, Marco; Sourkouni-Argirusi, Georgia; Kirschning, Andreas [Advanced Synthesis and Catalysis, 2003, vol. 345, # 5, p. 635 - 642]
[8]Norsikian, Stéphanie; Beretta, Margaux; Cannillo, Alexandre; Martin, Amélie; Retailleau, Pascal; Beau, Jean-Marie [Chemical Communications, 2015, vol. 51, # 49, p. 9991 - 9994]
[9]Sani, Monica; Lazzari, Paolo; Folini, Marco; Spiga, Marco; Zuco, Valentina; De Cesare, Michelandrea; Manca, Ilaria; Dall'Angelo, Sergio; Frigerio, Massimo; Usai, Igor; Testa, Andrea; Zaffaroni, Nadia; Zanda, Matteo [Chemistry - A European Journal, 2017, vol. 23, # 24, p. 5842 - 5850]
[10]Ocejo, Marta; Vicario, Jose L.; Badía, Dolores; Carrillo, Luisa; Reyes, Efraim [Synlett, 2005, # 13, p. 2110 - 2112]
[11]Lasheen, Deena S.; Ismail, Mohamed A.H.; Abou El Ella, Dalal A.; Ismail, Nasser S.M.; Eid, Sameh; Vleck, Susan; Glenn, Jeffrey S.; Watts, Andrew G.; Abouzid, Khaled A.M. [Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 10, p. 2742 - 2755]
[12]Colombo, Raffaele; Wang, Zhiyong; Han, Junyan; Balachandran, Raghavan; Daghestani, Hikmat N.; Camarco, Daniel P.; Vogt, Andreas; Day, Billy W.; Mendel, David; Wipf, Peter [Journal of Organic Chemistry, 2016, vol. 81, # 21, p. 10302 - 10320]
[13]Kempf [Journal of Organic Chemistry, 1986, vol. 51, # 21, p. 3921 - 3926]
[14]Pettit, George R.; Hogan, Fiona; Burkett, Douglas D.; Singh, Sheo B.; Kentoci, Darko; et al. [Heterocycles, 1994, vol. 39, # 1, p. 81 - 100]
[15]Braun, Hannes A.; Zall, Andrea; Brockhaus, Manfred; Schütz, Marco; Meusinger, Reinhard; Schmidt, Boris [Tetrahedron Letters, 2007, vol. 48, # 45, p. 7990 - 7993]
[16]Current Patent Assignee: ZHEJIANG YONGNING PHARMA - CN105198829, 2017, B Location in patent: Paragraph 0087-0089
[17]Bucci, Raffaella; Giofré, Sabrina; Clerici, Francesca; Contini, Alessandro; Pinto, Andrea; Erba, Emanuela; Soave, Raffaella; Pellegrino, Sara; Gelmi, Maria Luisa [Journal of Organic Chemistry, 2018, vol. 83, # 19, p. 11493 - 11501]
[18]Soucek, Milan; Urban, Jan [Collection of Czechoslovak Chemical Communications, 1995, vol. 60, # 4, p. 693 - 696]
[19]Shankar, Sreejith P.; Jagodzinska, Monika; Malpezzi, Luciana; Lazzari, Paolo; Manca, Ilaria; Greig, Iain R.; Sani, Monica; Zanda, Matteo [Organic and Biomolecular Chemistry, 2013, vol. 11, # 14, p. 2273 - 2287]
[20]Current Patent Assignee: C.H. Boehringer Sohn AG & Co. KG - US2010/144681, 2010, A1 Location in patent: Page/Page column 62
[21]Location in patent: experimental part Janssen, Michiel H. A.; Chesa Castellana, Juan F.; Jackman, Hayley; Dunn, Peter J.; Sheldon, Roger A. [Green Chemistry, 2011, vol. 13, # 4, p. 905 - 912]
[22]Hampton, Philip D.; Whealon, Matthew D.; Roberts, Lisa M.; Yaeger, Andrew A.; Boydson, Rick [Organic Process Research and Development, 2008, vol. 12, # 5, p. 946 - 949]
[23]Bera, Saurav; Panda, Gautam [Organic and Biomolecular Chemistry, 2014, vol. 12, # 23, p. 3976 - 3985]
[24]Daniliuc, Constantin G.; Gilmour, Ryan; Kehr, Gerald; Meyer, Stephanie; Scheidt, Felix; Thiehoff, Christian; Yilmaz, Gülay [Beilstein Journal of Organic Chemistry, 2018, vol. 14, p. 1021 - 1027]
[25]Stanfield, C. Freeman; Parker, James E.; Kanellis, Panayiotis [Journal of Organic Chemistry, 1981, vol. 46, # 23, p. 4797 - 4798]
[26]Delcamp, Jared H.; Brucks, Alexandria P.; White, M. Christina [Journal of the American Chemical Society, 2008, vol. 130, # 34, p. 11270 - 11271]
[27]Shirasaki, Yoshihisa; Miyashita, Hiroyuki; Yamaguchi, Masazumi; Inoue, Jun; Nakamura, Masayuki [Bioorganic and Medicinal Chemistry, 2005, vol. 13, # 14, p. 4473 - 4484]
[28]Current Patent Assignee: SENJU PHARMACEUTICAL CO.,LTD. - WO2005/56519, 2005, A1 Location in patent: Page/Page column 32-33
[29]Current Patent Assignee: OSAKA CITY UNIVERSITY - EP2647386, 2013, A1 Location in patent: Page/Page column
[30]Current Patent Assignee: OSAKA CITY UNIVERSITY - US9371359, 2016, B2 Location in patent: Page/Page column 34
[31]Current Patent Assignee: SENJU PHARMACEUTICAL CO.,LTD.; OSAKA CITY UNIVERSITY - US2019/314320, 2019, A1 Location in patent: Paragraph 0185
[32]Luly, Jay R.; Dellaria, Joseph F.; Plattner, Jacob J.; Soderquist, Jeffrey L.; Yi, Nwe [Journal of Organic Chemistry, 1987, vol. 52, # 8, p. 1487 - 1492]
[33]Karthikeyan, Ganesan; Perumal, Paramasivan T. [Synlett, 2003, # 14, p. 2249 - 2251]
[34]Ambreen, Nida; Kumar, Ravi; Wirth, Thomas [Beilstein Journal of Organic Chemistry, 2013, vol. 9, p. 1437 - 1442]
[35]Haghshenas, Pouyan; Gravel, Michel [Organic Letters, 2016, vol. 18, # 18, p. 4518 - 4521]
[36]Iizuka, Kinji; Kamijo, Tetsuhide; Herada, Hiromu; Akahane, Kenji; Kubota, Tetsuhiro; et al. [Journal of Medicinal Chemistry, 1990, vol. 33, # 10, p. 2707 - 2714]
[37]Dellaria Jr.; Maki [Tetrahedron Letters, 1986, vol. 27, # 21, p. 2337 - 2340]
[38]Tomioka, Kiyoshi; Kanai, Motomu; Koga, Kenji [Tetrahedron Letters, 1991, vol. 32, # 21, p. 2395 - 2398]
[39]Getman, Daniel P.; DeCrescenzo, Gary A.; Heintz, Robert M.; Reed, Kathryn L.; Talley, John J.; et al. [Journal of Medicinal Chemistry, 1993, vol. 36, # 2, p. 288 - 291]
[40]Thaisrivongs; Pals; Kati; Turner; Thomasco; Watt [Journal of Medicinal Chemistry, 1986, vol. 29, # 10, p. 2080 - 2087]
[41]Irako; Hamada; Shiori [Tetrahedron, 1992, vol. 48, # 35, p. 7251 - 7264]
[42]Konradi, Andrei W.; Kemp, Scott J.; Pedersen, Steven F. [Journal of the American Chemical Society, 1994, vol. 116, # 4, p. 1316 - 1323]
[43]Scholz; Billich; Charpiot; Ettmayer; Lehr; Rosenwirth; Schreiner; Gstach [Journal of Medicinal Chemistry, 1994, vol. 37, # 19, p. 3079 - 3089]
[44]Wyslouch, Aleksandra; Lisowski, Marek; Siemion, Ignacy Z. [Bulletin of the Polish Academy of Sciences: Chemistry, 1994, vol. 42, # 1, p. 117 - 130]
[45]Tietze; Burkhardt [Synthesis, 1994, # SPEC. ISS., p. 1331 - 1336]
[46]Sham, Hing L.; Betebenner, David A.; Wideburg, Norman E.; Kempf, Dale J.; Plattner, Jacob J.; et al. [Journal of Fluorine Chemistry, 1995, vol. 73, # 2, p. 221 - 224]
[47]Zygmunt, Jan; Gancarz, Roman; Lejczak, Barbara; Wieczorek, Piotr; Kafarski, Pawel [Bioorganic and Medicinal Chemistry Letters, 1996, vol. 6, # 24, p. 2989 - 2992]
[48]Gennari, Cesare; Longari, Chiara; Ressel, Stefano; Salom, Barbara; Mielgo, Antonia [European Journal of Organic Chemistry, 1998, # 6, p. 945 - 959]
[49]Ohno, Hiroaki; Toda, Ayako; Takemoto, Yoshiji; Fujii, Nobutaka; Ibuka, Toshiro [Journal of the Chemical Society. Perkin transactions I, 1999, # 20, p. 2949 - 2962]
[50]Lee, Kee-Young; Kim, Yong-Hyun; Park, Min-Sung; Oh, Chang-Young; Ham, Won-Hun [Journal of Organic Chemistry, 1999, vol. 64, # 26, p. 9450 - 9458]

7
[ 66605-57-0 ]
[ 103322-56-1 ]

Yield	Reaction Conditions	Operation in experiment
100%	With 5% rhodium-on-charcoal; hydrogen at 20℃;
100%	With 5% rhodium-on-charcoal; hydrogen In methanol at 20℃;	1 Synthesis of compound 7 S-Ztoophenylalaninol (2 g, 7.96 mmol) was dissolved in methanol and treated with rhodium on charcoal (5%; 100 mg) under H2 atmosphere overnight to reduce the phenyl ring. The solution was then passed through celite plug, and methanol was evaporated to give the pure product 7 in quantitative yield (2.01 g, quant).
95%	With 5% rhodium-on-charcoal; hydrogen In methanol; water at 60℃; for 16h;

	With hydrogen Yield given;
	With hydrogen for 18h;

Reference： [1]Kaur, Parminder; Chamberlin, A. Richard; Poulos, Thomas L.; Sevrioukova, Irina F. [Journal of Medicinal Chemistry, 2016, vol. 59, # 9, p. 4210 - 4220]
[2]Current Patent Assignee: UNIVERSITY OF CALIFORNIA - WO2017/44742, 2017, A1 Location in patent: Page/Page column 41
[3]Ager, David J.; Prakash, Indra [Organic Process Research and Development, 2003, vol. 7, # 2, p. 164 - 167]
[4]Harada; Tsubaki; Kamijo; Iizuka; Kiso [Chemical and Pharmaceutical Bulletin, 1989, vol. 37, # 9, p. 2570 - 2572]
[5]Iizuka; Kamijo; Harada; Akahane; Kubota; Umeyama; Kiso [Journal of the Chemical Society. Chemical communications, 1989, # 21, p. 1678 - 1680]

8
[ 83351-75-1 ]
[ 4248-19-5 ]
[ 102-93-2 ]
[ 66605-57-0 ]

Reference： [1]Journal of the Chemical Society. Chemical communications,1982,p. 639 - 640

9
[ 66605-57-0 ]
[ 98-59-9 ]
[ 141403-49-8 ]

Yield	Reaction Conditions	Operation in experiment
78%	With triethylamine; In dichloromethane; at 0 - 20℃;	S-Ztoophenylalaninol (1 g, 3.98 mmol) was dissolved in DCM. To this solution, triethylamine and />-toluenesulphonyl chloride were added slowly at 0 C. The reaction was then allowed to stir at room temperature overnight. After reaction completion, DCM was evaporated and the crude reaction mixture was purified using column chromatography. The pure product 13a was obtained as white fluffy solid in 78% yield (1.26g). The pure product 13b was obtained as white solid in 81% yield
38%	With triethylamine; In dichloromethane; at 20℃; for 3.0h;	Boc- L-phenylalaninol (1.01 g, 4.0 mmol, 1.0 equiv.) and/7-toluenesulfonyl chloride (0.92 g, 4.8 mmol, 1.2 equiv.) were dissolved in dichloromethane (20 mL) and to the solution was added triethylamine (0.84 mL, 6.0 mmol, 1.5 equiv.) at room temperature. The resulting mixture was stirred for 3h, and then the reaction was quenched with saturated ammonium chloride solution. The phases were separated and the water layer was extracted with ether twice. The combined organic phase was washed once with brine, dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was chromatographed on silica gel (0- 20 % ethyl acetate in hexane) to afford 231 as a white solid (0.61 g, 38%). Purity 99 % (HPLC).
38%	With triethylamine; In dichloromethane; at 20℃; for 3.0h;	Boc- L-phenylalaninol (1.01 g, 4.0 mmol, 1.0 equiv.) and />toluenesulfonyl chloride (0.92 g, 4.8 mmol, 1.2 equiv.) were dissolved in dichloromethane (20 mL) and to the solution was added triethylamine (0.84 mL, 6.0 mmol, 1.5 equiv.) at room temperature. The resulting mixture was stirred for 3h, and then the reaction was quenched with saturated ammonium chloride solution. The phases were separated and the water layer was extracted with ether twice. The combined organic phase was washed once with brine, dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was chromatographed on silica gel (0- 20 % ethyl acetate in hexane) to afford 231 as a white solid (0.61 g, 38%). Purity 99 % (HPLC).

38%	With triethylamine; In dichloromethane; at 20℃; for 3.0h;	10250] Boc-E-phenylalaninol (1.01 g, 4.0 mmol, 1.0 equiv.) and p-toluenesulfonyl chloride (0.92 g, 4.8 mmol, 1.2 equiv.) were dissolved in dichloromethane (20 mE) and to the solution was added triethylamine (0.84 mE, 6.0 mmol, 1.5 equiv.) at room temperature. The resulting mixture was stirred for 3 h, and then the reaction was quenched with saturated ammonium chloride solution. The phases were separated and the water layer was extracted with ether twice. The combined organic phase was washed once with brine, dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was chromatographed on silica gel (0-20% ethyl acetate in hexane) to afford 231 as a white solid (0.61 g, 38%). Purity 99% (HPEC).
		Synthesis of Synthesis of Toluene-4-sulfonicacid(S)-2-tert-butoxycarbonylamino-3- phenyl-propyl ester [A014] To a solution of Boc-L-phenylalaninol (0.5 g, 1.989 mmol) in DCM (10 mL) at 0C was added triethylamine (0.83 mL, 5.968 mmol). The reaction mixture was stirred at this temperature for 5minutes. para-Toluenesufonyl chloride (2.188 mmol, 0.42 g) was added dropwise as a solution in DCM (5 mL), and the reaction mixture was allowed to warm up to room temperature slowly. The reaction mixture stirred at room temperature for 4 hours. The reaction mixture was diluted with DCM (20 mL) and washed with water. Layers separated and the organic layer dried over anhydrous magnesium sulphate. The DCM was evaporated to dryness under reduced pressure to afford the title compound [A014] as a clear oil (0.8g). No further purification was carried out and the crude product was used immediately in the next step.
	With dmap; triethylamine; In dichloromethane; at 0 - 25℃; for 3.0h;	General procedure: To a stirred solution of N-Boc protected amino alcohol 9 (0.5mg, 1.98mmol) in CH2Cl2 (5mL) were added dry triethylamine (0.3mL, 2.37mmol) and p-toluenesulfonyl chloride (0.452g, 2.37mmol) in the presence of a catalytic amount of 4-dimethylaminopyridine (0.024g,10mol%) at 0C. The reaction mixture was stirred at 25C for 3h and then quenched by addition of 10% NaHCO3. The aqueous layer was extracted with CH2Cl2 (3×20mL) and the combined organic layers were dried over anhydrous Na2SO4, and concentrated to give the crude tosylate, which was then dissolved in dry THF (5mL), and added dropwise to a suspension of LiAlH4 (0.225g, 3mmol) in dry THF (10mL). The mixture was refluxed for 4h and then cooled to 0C after which the excess LiAlH4 was quenched by the addition of EtOAc. It was then treated with aq. 20% NaOH (0.5mL). The white precipitate which formed was filtered off, and the residue was washed with EtOAc (3×10mL). The combined EtOAc layers were dried over anhydrous Na2SO4, and the solvent was evaporated under reduced pressure. The crude product was purified by column chromatography over silica gel using CHCl3 as the eluent to afford the corresponding pure N-methyl amine 11
	With dmap; triethylamine; In dichloromethane;	General procedure: To a solution of intermediates 10a-g (1 equiv) in dichloromethane, TsCl (1.2 equiv), DMAP (0.2 equiv) and trimethylamine(3 equiv) were added. The solutionwas stirred at 20 C.The reaction was followed by TLC and quenched with water. Theorganic phase was washed with citric acid (1 N) and saturatedNaHCO3 then dried over Na2SO4 and filtered. The filtrate wasconcentrated and purified by a silica column to afford compounds11a-g as a white solid.

Reference： [1]Tetrahedron Letters,1995,vol. 36,p. 2505 - 2508
[2]Tetrahedron,1997,vol. 53,p. 4769 - 4778
[3]European Journal of Medicinal Chemistry,1989,vol. 24,p. 503 - 510
[4]Heterocycles,2009,vol. 77,p. 865 - 872
[5]Organic and Biomolecular Chemistry,2014,vol. 12,p. 3976 - 3985
[6]Journal of the Chemical Society. Perkin transactions I,1988,p. 1645 - 1652
[7]Journal of Medicinal Chemistry,2016,vol. 59,p. 4210 - 4220
[8]Patent: WO2017/44742,2017,A1 .Location in patent: Page/Page column 42; 43
[9]Journal of Organic Chemistry,2001,vol. 66,p. 4904 - 4914
[10]European Journal of Medicinal Chemistry,1993,vol. 28,p. 47 - 61
[11]Patent: WO2008/22345,2008,A2 .Location in patent: Page/Page column 47
[12]Patent: WO2009/105782,2009,A1 .Location in patent: Page/Page column 44
[13]Patent: US2015/284352,2015,A1 .Location in patent: Paragraph 0249; 0250
[14]Chemistry Letters,1992,p. 2409 - 2412
[15]Journal of Medicinal Chemistry,1992,vol. 35,p. 1259 - 1266
[16]Journal of Organic Chemistry,1997,vol. 62,p. 6754 - 6759
[17]Journal of Organic Chemistry,1998,vol. 63,p. 7764 - 7769
[18]Angewandte Chemie - International Edition,2000,vol. 39,p. 2752 - 2754
[19]Tetrahedron,2007,vol. 63,p. 9758 - 9763
[20]Synlett,2007,p. 1893 - 1896
[21]Journal of Peptide Science,2011,vol. 17,p. 527 - 532
[22]Patent: WO2014/52699,2014,A1 .Location in patent: Page/Page column 222-223
[23]Tetrahedron Asymmetry,2015,vol. 26,p. 67 - 72
[24]Organometallics,2014,vol. 33,p. 6452 - 6465
[25]RSC Advances,2017,vol. 7,p. 15742 - 15746
[26]European Journal of Medicinal Chemistry,2019,vol. 177,p. 374 - 385

10
[ 72155-45-4 ]
[ 66605-57-0 ]

Yield	Reaction Conditions	Operation in experiment
91%	Stage #1: Boc-L-phenylalaninal With 1-Methylpyrrolidine; 2-chloro-5-fluorophenylboronic acid; phenylsilane at 20℃; for 16h; Inert atmosphere; Stage #2: With sodium hydroxide In water at 20℃; for 2h; chemoselective reaction;
62%	With sodium tetrahydroborate In methanol at 20℃; for 0.25h; Inert atmosphere;
	With sodium tetrahydroborate In 1,2-dimethoxyethane Ambient temperature;

	With lithium borohydride
	With sodium tetrahydroborate In methanol at 0℃; for 1h;
	With sodium tetrahydroborate In methanol

Reference： [1]Chardon, Aurélien; Rouden, Jacques; Blanchet, Jérôme [European Journal of Organic Chemistry, 2019, vol. 2019, # 5, p. 995 - 998]
[2]Holan, Martin; Jahn, Ullrich [Organic Letters, 2014, vol. 16, # 1, p. 58 - 61]
[3]Fehrentz, Jean-Alain; Pothion, Catherine; Califano, Jean-Christophe; Loffet, Albert; Martinez, Jean [Tetrahedron Letters, 1994, vol. 35, # 48, p. 9031 - 9034]
[4]Dias, Luiz C.; Fattori, Juliana; Perez, Carla C.; de Oliveira, Vanda M.; Aguilar, Andrea M. [Tetrahedron, 2008, vol. 64, # 25, p. 5891 - 5903]
[5]Wu, Yan-Chao; Zhu, Jieping [Journal of Organic Chemistry, 2008, vol. 73, # 23, p. 9522 - 9524]
[6]Norsikian, Stéphanie; Beretta, Margaux; Cannillo, Alexandre; Auvray, Marie; Martin, Amélie; Retailleau, Pascal; Iorga, Bogdan I.; Beau, Jean-Marie [European Journal of Organic Chemistry, 2017, vol. 2017, # 14, p. 1940 - 1951]

11
[ 51987-73-6 ]
[ 72155-45-4 ]
[ 66605-57-0 ]

Yield	Reaction Conditions	Operation in experiment
96%	With diisobutylaluminium hydride In hexane; dichloromethane at -78℃; for 0.1h;

Reference： [1]Camplo; Niddam; Barthelemy; Faury; Mourier; Simon; Charvet; Trabaud; Graciet; Chermann; Kraus [European Journal of Medicinal Chemistry, 1995, vol. 30, # 10, p. 789 - 800]

12
[ 66605-57-0 ]
[ 104-15-4 ]
[ 141403-49-8 ]

Reference： [1]Tetrahedron Letters,1999,vol. 40,p. 2629 - 2632

13
[ 161417-28-3 ]
[ 66605-57-0 ]
[ 882170-26-5 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 1679 - 1685

14
[ 66605-57-0 ]
[ 17585-69-2 ]

Reference： [1]Tetrahedron,2005,vol. 61,p. 3403 - 3417
[2]Tetrahedron Letters,2004,vol. 45,p. 2467 - 2471

15
[ 66605-57-0 ]
[ 26250-86-2 ]

Reference： [1]Journal of Organic Chemistry,1998,vol. 63,p. 7764 - 7769

16
[ 66605-57-0 ]
[ 15099-85-1 ]

Reference： [1]Journal of Organic Chemistry,1998,vol. 63,p. 7764 - 7769

17
[ 66605-57-0 ]
[ 146552-72-9 ]

Reference： [1]Tetrahedron,1996,vol. 52,p. 14507 - 14514
[2]Journal of Chemical Research, Miniprint,1992,p. 3117 - 3132
[3]Journal of Medicinal Chemistry,1994,vol. 37,p. 1810 - 1822
[4]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 2877 - 2879
[5]Patent: US2013/274269,2013,A1
[6]Heterocycles,2015,vol. 90,p. 950 - 966
[7]Patent: US2015/284352,2015,A1
[8]Patent: CN103848778,2016,B
[9]Patent: US2008/114167,2008,A1
[10]Patent: WO2009/105782,2009,A1

18
[ 66605-57-0 ]
[ 146476-38-2 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: pyridine / 0 °C 2: n-BuLi / tetrahydrofuran / -20 °C 3: CF₃COOH
	Multi-step reaction with 3 steps 1: triethylamine / dichloromethane / 0 - 20 °C / Inert atmosphere; Glovebox; Schlenk technique 2: tetrahydrofuran / 16 h / -40 - 20 °C / Inert atmosphere; Glovebox; Schlenk technique 3: trifluoroacetic acid / dichloromethane / 15 h / 0 - 20 °C / Inert atmosphere; Glovebox; Schlenk technique
	Multi-step reaction with 3 steps 1: triethylamine / dichloromethane 2: tetrahydrofuran 3: trifluoroacetic acid / dichloromethane

Reference： [1]Hiroi, Kunio; Haraguchi, Mitsuhiro; Masuda, Yoko; Abe, Jun [Chemistry Letters, 1992, # 12, p. 2409 - 2412]
[2]Sonnenberg, Jessica F.; Lough, Alan J.; Morris, Robert H. [Organometallics, 2014, vol. 33, # 22, p. 6452 - 6465]
[3]Wang, Kaiye; Xiang, Yanan; Shi, Zhujun; Wang, Hongyu; Li, Na; Tang, Bo [Organic and Biomolecular Chemistry, 2019, vol. 17, # 26, p. 6351 - 6354]

19
[ 66605-57-0 ]
[ 131288-67-0 ]

Reference： [1]Chemical and Pharmaceutical Bulletin,1989,vol. 37,p. 2570 - 2572

20
[ 66605-57-0 ]
[ 135383-60-7 ]

Reference： [1]Tetrahedron Letters,1991,vol. 32,p. 2395 - 2398

21
[ 66605-57-0 ]
[ 110417-88-4 ]

Reference： [1]Tetrahedron Letters,1991,vol. 32,p. 2395 - 2398

22
[ 130115-85-4 ]
[ 66605-57-0 ]
3-bromo-2-chloro-5-((S)-2-methyl-3-phenyl-propoxy)-pyridine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
87%	With triphenylphosphine; diethylazodicarboxylate; In tetrahydrofuran; at 0 - 20℃; for 1h;	DEAD (0.30 mL, 1.87 mmol) was added to a solution of 4-bromo-5-chloro-3- hydroxypyridine (243 mg, 1.17 mmol, Koch, V. Schnatterer, S. Synthesis, 1990, 499-501), compound of Example 1 (a) (440 mg, 1.80 mmol) and Ph3P (460 mg, 1.80 mmol) in THF (10 mL) at 0 C. The resulting mixture was warmed up to room temperature and stirred for 1 h. The reaction was complete indicated by TLC. The reaction mixture was concentrated and the residue was purified by flash column chromatography (hexane/EtOAc 9: 1) to give a white solid (450 mg, 87%).

Reference： [1]Patent: WO2005/85227,2005,A1 .Location in patent: Page/Page column 37; 76

23
[ 38862-25-8 ]
[ 72155-45-4 ]
[ 66605-57-0 ]

Yield	Reaction Conditions	Operation in experiment
	With lithium borohydride In tetrahydrofuran	4.a (a) (a) N-[(1,1-Dimethylethoxy)carbonyl]-L-phenylalaninal To a solution of lithium borohydride (940 mg. 43.2 mmole) in dry tetrahydrofuran (90 ml.) cooled in an ice-bath under nitrogen is added a solution containing N-[(1,1-dimethylethoxy)carbonyl]-L-phenylalanine, N-hydroxysuccinimide ester (6.0 g., 16.6 mmole) [prepared according to the procedure of Anderson et al., JACS, Vol. 86, p.1839 (1964)]in tetrahydrofuran (60 ml.). The addition is carried out over a period of 5 minutes. After an additional 20 minutes at 0°, the reaction mixture is poured into 1l. of cold 10% potassium bisulfate. The mixture is extracted with ethyl acetate (4*150 ml) and the combined organic extracts are rinsed with saturated sodium bicarbonate, water, and brine, dried over magnesium sulfate, and concentrated in vacuo to give 3.8 g. of crude product. Flash chromatography (Merck 9385 silica gel, 250 g.) eluding with chloroform:methanol (100:1, 50:1, and finally 25:1) gives 2.4 g. of purified product. Recrystallization from etherhexane gives 1.9 g. of (S)-2-[[(1,1-dimethylethoxy)carbonyl]amino]-2-phenylmethyl-1-ethanol; m.p. 95°-96°; [α]D=- 27.5° (c=1, methanol). TLC (silica gel; chloroform:methanol:acetic acid, 25:1:1) Rf =0.54. Anal. calc'd. for C14 H21 NO3 C, 66.90; H, 8.42; N, 5.57 Found: C, 67.02; H, 8.49; N, 5.23.

Reference： [1]Current Patent Assignee: BRISTOL-MYERS SQUIBB CO - US4885292, 1989, A

24
[ 66605-57-0 ]
[ 7143-01-3 ]
(2S)-2-[(tert-butoxycarbonyl)amino]-3-phenylpropyl methanesulfonate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
70%	With N-ethyl-N,N-diisopropylamine In dichloromethane at 0℃; for 3h;	23 Preparation of (S)-2-(tert-butoxycarbonylamino)-3-phenylpropyl methanesulfonate To the mixture of 2.51 g (S)-tert-butyl 1-hydroxy-3-phenylpropan-2-ylcarbamate (10.0 mmol, 1.00 equiv) and 2.58 g N,N-diisopropylethylamine (20.0 mmol, 2.00 equiv) in 30 mL dichloromethane was added 1.74 g methanesulfonic anhydride (10.0 mmol, 1.0 equiv). The mixture was stirred at 0 °C for 3 hours. The mixture was diluted with 100 mL water and washed with 3 x 100 mL volumes of ethyl acetate. The organic phase was concentrated and the residue was purified by column chromatography on silica gel (petroleum ether:ethyl acetate (10:1, v:v)) to yield 2.30 g (S)-2-(tert-butoxycarbonylamino)-3-phenylpropyl methanesulfonate as a light yellow oil (70 % yield). MS (ESI+) m/z 330 [M+H]+.
	With triethylamine In tetrahydrofuran at 0℃; for 0.5h;	1.2.A To a 0° C. stirred solution of (S)-1-benzyl-2-hydroxy-ethyl)-carbamic acid tert-butyl ester (5.00 g, 19.9 mmol), triethylamine (6.03 g, 59.7 mmol) in anhydrous THF under nitrogen was added methanesulfonic anhydride (4.50 g, 25.9 mmol). After 20 minutes the ice bath was removed and the reaction was allowed to proceed for about 10 minutes. The volatiles were evaporated and to the residue was added sodium azide (6.47 g, 99.5 mmol) and anhydrous DMSO (50 mL). The mixture was heated at 50° C. overnight, cooled, mixed with water (100 mL) and extracted with ethyl acetate (100 mL×2). Evaporation of the extracts gave a residue that was purified by chromatography (silica gel, 0% to 25% ethyl acetate/hexane) to give the title compound (3.56 g, 65%) which was pure by LC/MS(+APCI) m/z 177 (M+H-BOC).

Reference： [1]Current Patent Assignee: VINCERE BIOSCIENCES - WO2021/50992, 2021, A1 Location in patent: Paragraph 00573-00574
[2]Current Patent Assignee: ALCON, INC. - US2007/149548, 2007, A1 Location in patent: Page/Page column 7

25
[ 1131041-73-0 ]
[ 66605-57-0 ]
[ 1131042-09-5 ]

Yield	Reaction Conditions	Operation in experiment
92%	With di-isopropyl azodicarboxylate; triphenylphosphine In tetrahydrofuran at 15 - 20℃;	1.h Triphenylphosphine (1.83 g, 7.0 mmol) was dissolved in THF (25 ml_). The resulting solution was cooled in a water/ice bath to 15°C, and stirred for 10 min. Added slowly to the stirring mixture was diisopropylazodicarboxylate (1.4 ml_, 7.0 mmol) and the mixture was stirred for 30 min. In a separate beaker were mixed 1 ,1- dimethylethyl (5-bromo-6-chloro-3-hydroxy-2-pyridinyl)carbamate (1.62 g, 5.0 mmol) and 1 ,1-dimethylethyl [(1 S)-2-hydroxy-1-(phenylmethyl)ethyl]carbamate (1.76 g, 7.0 mmol) in THF (25 ml_), and this mixture added via dropping funel over 1 min. The mixture was stirred at 15°C for 30 min, and then for 90 min at room temperature. The mixture was diluted with isopropanol (25 ml.) and stirred for 30 min, after which time the contents were concentrated in vacuo. The residue obtained was purified by flash chromatography (eluant: 5% to 100% ethyl acetate gradient in chloroform/hexane (1 :1 )) to afford the title compound as a solid (2.55 g, 92%). MS(ES)+ m/e 595 [M+H]+. This material was carried over to next step without further purification.

Reference： [1]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2009/32651, 2009, A1 Location in patent: Page/Page column 8; 35

26
[ 130115-85-4 ]
[ 66605-57-0 ]
[ 352704-97-3 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2010,vol. 20,p. 673 - 678

27
[ 66605-57-0 ]
[ 1088965-37-0 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1.1: di-isopropyl azodicarboxylate; triphenylphosphine / methanol; toluene / 42 - 60 °C 1.2: 2 h / 60 °C 2.1: aluminum (III) chloride / 22 h / -5 °C 2.2: 35 - 50 °C 2.3: 18 h / 65 °C 3.1: N-ethyl-N,N-diisopropylamine / acetonitrile / 5 - 8 °C 4.1: tetrabutylammomium bromide; sodium hydrogencarbonate / acetonitrile / 26 h / Reflux; Large scale reaction 5.1: hydrazine hydrate / ethanol; tert-butyl methyl ether / 16 h / 40 °C 5.2: 40 °C 6.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine / dichloromethane / 12 h / 20 °C
	Multi-step reaction with 6 steps 1.1: di-isopropyl azodicarboxylate; triphenylphosphine / methanol; toluene / 42 - 60 °C 1.2: 2 h / 60 °C 2.1: aluminum (III) chloride / 22 h / -5 °C 2.2: 35 - 50 °C 2.3: 18 h / 65 °C 3.1: N-ethyl-N,N-diisopropylamine / acetonitrile / 5 - 8 °C 4.1: tetrabutylammomium bromide; sodium hydrogencarbonate / acetonitrile / 26 h / Reflux; Large scale reaction 5.1: hydrazine hydrate / ethanol; tert-butyl methyl ether / 16 h / 40 °C 5.2: 40 °C 6.1: 2-methyltetrahydrofuran / 22 °C
	Multi-step reaction with 7 steps 1.1: di-isopropyl azodicarboxylate; triphenylphosphine / methanol; toluene / 42 - 60 °C 1.2: 2 h / 60 °C 2.1: aluminum (III) chloride / 22 h / -5 °C 2.2: 35 - 50 °C 2.3: 18 h / 65 °C 3.1: N-ethyl-N,N-diisopropylamine / acetonitrile / 5 - 8 °C 4.1: tetrabutylammomium bromide; sodium hydrogencarbonate / acetonitrile / 26 h / Reflux; Large scale reaction 5.1: hydrazine hydrate / ethanol; tert-butyl methyl ether / 16 h / 40 °C 5.2: 40 °C 6.1: dipotassium hydrogenphosphate / 2-methyltetrahydrofuran; water / 10 °C 7.1: 2-methyltetrahydrofuran; water / 4 h / 40 °C

	Multi-step reaction with 8 steps 1.1: triethylamine / ethyl acetate / 0 - 4 °C / Large scale reaction 2.1: tetrabutylammomium bromide / Isopropyl acetate / 23 h / 35 °C / Large scale reaction 3.1: hydrogenchloride; water / methanol / 3.25 h / 60 °C 4.1: aluminum (III) chloride / 22 h / -5 °C 4.2: 35 - 50 °C 4.3: 18 h / 65 °C 5.1: N-ethyl-N,N-diisopropylamine / acetonitrile / 5 - 8 °C 6.1: tetrabutylammomium bromide; sodium hydrogencarbonate / acetonitrile / 26 h / Reflux; Large scale reaction 7.1: hydrazine hydrate / ethanol; tert-butyl methyl ether / 16 h / 40 °C 7.2: 40 °C 8.1: 2-methyltetrahydrofuran / 22 °C
	Multi-step reaction with 8 steps 1.1: triethylamine / ethyl acetate / 0 - 4 °C / Large scale reaction 2.1: tetrabutylammomium bromide / Isopropyl acetate / 23 h / 35 °C / Large scale reaction 3.1: hydrogenchloride; water / methanol / 3.25 h / 60 °C 4.1: aluminum (III) chloride / 22 h / -5 °C 4.2: 35 - 50 °C 4.3: 18 h / 65 °C 5.1: N-ethyl-N,N-diisopropylamine / acetonitrile / 5 - 8 °C 6.1: tetrabutylammomium bromide; sodium hydrogencarbonate / acetonitrile / 26 h / Reflux; Large scale reaction 7.1: hydrazine hydrate / ethanol; tert-butyl methyl ether / 16 h / 40 °C 7.2: 40 °C 8.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine / dichloromethane / 12 h / 20 °C
	Multi-step reaction with 9 steps 1.1: triethylamine / ethyl acetate / 0 - 4 °C / Large scale reaction 2.1: tetrabutylammomium bromide / Isopropyl acetate / 23 h / 35 °C / Large scale reaction 3.1: hydrogenchloride; water / methanol / 3.25 h / 60 °C 4.1: aluminum (III) chloride / 22 h / -5 °C 4.2: 35 - 50 °C 4.3: 18 h / 65 °C 5.1: N-ethyl-N,N-diisopropylamine / acetonitrile / 5 - 8 °C 6.1: tetrabutylammomium bromide; sodium hydrogencarbonate / acetonitrile / 26 h / Reflux; Large scale reaction 7.1: hydrazine hydrate / ethanol; tert-butyl methyl ether / 16 h / 40 °C 7.2: 40 °C 8.1: dipotassium hydrogenphosphate / 2-methyltetrahydrofuran; water / 10 °C 9.1: 2-methyltetrahydrofuran; water / 4 h / 40 °C

Reference： [1]Bellingham, Richard; Buswell, A. Mark; Choudary, Bernie M.; Gordon, Andrew H.; Moore, Steve O.; Peterson, Matthew; Sasse, Mike; Shamji, Amin; Urquhart, Michael W. J. [Organic Process Research and Development, 2010, vol. 14, # 5, p. 1254 - 1263]
[2]Bellingham, Richard; Buswell, A. Mark; Choudary, Bernie M.; Gordon, Andrew H.; Moore, Steve O.; Peterson, Matthew; Sasse, Mike; Shamji, Amin; Urquhart, Michael W. J. [Organic Process Research and Development, 2010, vol. 14, # 5, p. 1254 - 1263]
[3]Bellingham, Richard; Buswell, A. Mark; Choudary, Bernie M.; Gordon, Andrew H.; Moore, Steve O.; Peterson, Matthew; Sasse, Mike; Shamji, Amin; Urquhart, Michael W. J. [Organic Process Research and Development, 2010, vol. 14, # 5, p. 1254 - 1263]
[4]Bellingham, Richard; Buswell, A. Mark; Choudary, Bernie M.; Gordon, Andrew H.; Moore, Steve O.; Peterson, Matthew; Sasse, Mike; Shamji, Amin; Urquhart, Michael W. J. [Organic Process Research and Development, 2010, vol. 14, # 5, p. 1254 - 1263]
[5]Bellingham, Richard; Buswell, A. Mark; Choudary, Bernie M.; Gordon, Andrew H.; Moore, Steve O.; Peterson, Matthew; Sasse, Mike; Shamji, Amin; Urquhart, Michael W. J. [Organic Process Research and Development, 2010, vol. 14, # 5, p. 1254 - 1263]
[6]Bellingham, Richard; Buswell, A. Mark; Choudary, Bernie M.; Gordon, Andrew H.; Moore, Steve O.; Peterson, Matthew; Sasse, Mike; Shamji, Amin; Urquhart, Michael W. J. [Organic Process Research and Development, 2010, vol. 14, # 5, p. 1254 - 1263]

28
[ 23530-40-7 ]
[ 66605-57-0 ]
[ 1246617-32-2 ]

Yield	Reaction Conditions	Operation in experiment
	With triphenylphosphine; diethylazodicarboxylate; In tetrahydrofuran; toluene; at 20℃; for 3h;	Example 16 First StepCompound 50A (1.00 g, 3.98 mmol), triphenylphosphine (1.15 g, 4.48 mmol) and <strong>[23530-40-7]N-methyl-2-nitrobenzenesulfonamide</strong> (860 mg, 3.98 mmol) were added to THF (10 ml), and diethyl azodicarboxylate (2.2M in toluene, 1.99 ml, 4.38 mmol) was added dropwise at room temperature. After stirring at room temperature for 3 hours, the solvent was distilled off under reduced pressure. The resulting crude product was purified by silica gel column chromatography (n-hexane-ethyl acetate, 1:1, v/v) to obtain 710 mg of Compound 50B as a colorless gummy substance.

Reference： [1]Patent: US2012/22251,2012,A1 .Location in patent: Page/Page column 41

29
[ 33574-02-6 ]
[ 66605-57-0 ]
(S)-1-(cyclopropylmethoxy)-3-phenylpropan-2-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
40%	Stage #1: cyclopropylmethyl iodide; (S)-N-tert-butoxycarbonyl-2-amino-3-phenylpropanol With sodium hydride In N,N-dimethyl-formamide at 0 - 25℃; for 6h; Inert atmosphere; Stage #2: With trifluoroacetic acid In dichloromethane at 25℃; for 16h;	1; 3.2.8 (S)-l-(cvclopropylmethoxy)-3-phenylpropan-2-amine (A) To a solution, under argon, of 4.00 g (15.92 mmol, 1 eq.) of 21 in 40 mL of anhydrous DMF at 0 °C were added 0.955 g (23.87 mmol, 1.5 eq.) of sodium hydride 60wt% and 5.80 mL (31.8 mmol, 2.0 eq.) of lodomethylcyclopropane. The suspension was then stirred at 25°C for 4 hours. Another 0.32 g (7.96 mmol, 0.5 eq.) of sodium hydride 60wt% were added and the suspension was stirred for 2 hours. The mixture was treated with a saturated solution of ammonium chloride and extracted with dichloromethane. The organic layer was dried over Na2S04, filtered and concentrated in vacuo. The residue was filtered on silica gel (cyclohexane / AcOEt 9: 1) to afford 5.13 g of a yellow oil. The oil was readily dissolved in dichloromethane (75 mL) and treated with trifluoroacetic acid (13 mL). The mixture was stirred at 25 °C for 16 hours. Aqueous sodium hydroxide (1M) was added carefully until neutral pH was reached. The organic layer was dried over Na2S04, filtered and concentrated in vacuo. The residue was purified by flash chromatography (AcOEt + 1% of NH3(aq)to AcOEt/MeOH 98/2 + 1% of NH3(aq)) to afford 1.3 g of A as a yellow oil. Yield 40%.NMR 1H (400 MHz; CDC13) δΗ7.32-7.28 (2H, m), 7.23-7.20 (3H, m), 3.45 (1H, m), 3.31-3.25 (4H, m), 2.80 (1H, dd, J = 13.4, 4.8 Hz), 2.59 (1H, dd, J = 13.4, 7.6 Hz), 1.72 (2H, s), 2.80 (1H, dd, J = 13.4, 4.8 Hz), 1.06 (1H, m), 0.53 (2H, m), 0.20 (2H, m). NMR13C (100 MHz; CDC13) 5C139.0, 128.4, 128.6, 126.5, 76.1, 75.1, 52.6, 40.8, 10.7, 3.16, 3.11. IR vmax3081, 3024, 3006, 2923, 2858, 1092, 1024, 830, 743, 701 cm"1. MS (ESI+): calcd for C13H20NO [(M+H)+]: 206,2; Found: 206,2.

Reference： [1]Current Patent Assignee: CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE; CENTRE HOSPITALIER UNIVERSITAIRE D'AMIENS-PICARDIE; UNIVERSITY OF PICARDIE JULES VERNE - WO2019/86614, 2019, A1 Location in patent: Page/Page column 48; 73; 79

30
[ 1207294-92-5 ]
[ 66605-57-0 ]
C₃₅H₄₆N₂O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine In 2-methoxy-2-methylpropane at 23℃; for 0.25h; Inert atmosphere;

Reference： [1]Macmillan, David W. C.; Sakai, Holt A. [Journal of the American Chemical Society, 2022, vol. 144, # 14, p. 6185 - 6192]

31
[ 1895006-01-5 ]
[ 66605-57-0 ]
[ 2795139-79-4 ]

Yield	Reaction Conditions	Operation in experiment
69%	Stage #1: (S)‐tert‐butyl 1‐hydroxy‐3‐phenylpropan‐2‐ylcarbamate With pyridine; 5,7-di-tert-butyl-3-phenylbenzo[d]oxazol-3-ium tetrafluoroborate In 2-methoxy-2-methylpropane at 20℃; for 0.25h; Inert atmosphere; Stage #2: Umemoto’s reagent With Quinuclidine; [Cu(terpy)Cl₂]; C₃₆H₂₂F₁₀IrN₄O₂⁽¹⁺⁾*F₆P^(1-); tetra-n-butyl-ammonium chloride In dimethyl sulfoxide at 20℃; for 8h; Irradiation; Inert atmosphere; Sealed tube;

Reference： [1]Intermaggio, Nicholas E.; Millet, Agustin; Davis, Dali L.; MacMillan, David W. C. [Journal of the American Chemical Society, 2022, vol. 144, # 27, p. 11961 - 11968]

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
{[ item.p_purity ]}	{[ item.pr_size ]}	{[ getRatePrice(item.pr_usd, 1,1) ]} {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]}	{[ getRatePrice(item.pr_usd, 1,1) ]}	Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} {[ getRatePrice(item.pr_usd,1,item.mem_rate) ]}	{[ item.pr_usastock ]}	Inquiry -	{[ item.pr_chinastock ]}	Inquiry -

CAS No. :	66605-57-0	MDL No. :	MFCD00076976
Formula :	C₁₄H₂₁NO₃	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	LDKDMDVMMCXTMO-LBPRGKRZSA-N
M.W :	251.32	Pubchem ID :	2733675
Synonyms :		Chemical Name :	Boc-Phenylalaninol

Num. heavy atoms :	18
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.5
Num. rotatable bonds :	7
Num. H-bond acceptors :	3.0
Num. H-bond donors :	2.0
Molar Refractivity :	70.73
TPSA :	58.56 Å²

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.22 cm/s

Log Po/w (iLOGP) :	2.64
Log Po/w (XLOGP3) :	2.27
Log Po/w (WLOGP) :	2.11
Log Po/w (MLOGP) :	2.07
Log Po/w (SILICOS-IT) :	2.06
Consensus Log Po/w :	2.23

[ CAS No. 66605-57-0 ] {[proInfo.proName]}

Quality Control of [ 66605-57-0 ]

Related Doc. of [ 66605-57-0 ]

Product Details of [ 66605-57-0 ]

Calculated chemistry of [ 66605-57-0 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 66605-57-0 ]

Application In Synthesis of [ 66605-57-0 ]

[ 66605-57-0 ] Synthesis Path-Upstream 1~5

[ 66605-57-0 ] Synthesis Path-Downstream 1~31

Related Functional Groups of
[ 66605-57-0 ]

Amino Acid Derivatives

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

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

Log S (ESOL) :	-2.61
Solubility :	0.613 mg/ml ; 0.00244 mol/l
Class :	Soluble
Log S (Ali) :	-3.14
Solubility :	0.184 mg/ml ; 0.00073 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-3.64
Solubility :	0.058 mg/ml ; 0.000231 mol/l
Class :	Soluble

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	0.0
Synthetic accessibility :	2.65

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P305+P351+P338	UN#:	N/A
Hazard Statements:	H315-H319-H335	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