[ CAS No. 16881-33-7 ] {[proInfo.proName]}

Name: 16881-33-7|tert-Butyl ((benzyloxy)carbonyl)-L-tyrosinate|97%
Brand: Ambeed
SKU: A239029
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2D 3D

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Quality Control of [ 16881-33-7 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 16881-33-7 ]

SDS Specification

Alternatived Products of [ 16881-33-7 ]

Product Details of [ 16881-33-7 ]

CAS No. :	16881-33-7	MDL No. :	MFCD00191166
Formula :	C₂₁H₂₅NO₅	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	-
M.W :	371.43	Pubchem ID :	-
Synonyms :		Chemical Name :	tert-Butyl ((benzyloxy)carbonyl)-L-tyrosinate

Calculated chemistry of [ 16881-33-7 ]

Physicochemical Properties

Num. heavy atoms :	27
Num. arom. heavy atoms :	12
Fraction Csp3 :	0.33
Num. rotatable bonds :	10
Num. H-bond acceptors :	5.0
Num. H-bond donors :	2.0
Molar Refractivity :	102.17
TPSA :	84.86 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	No
P-gp substrate :	Yes
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.41 cm/s

Lipophilicity

Log Po/w (iLOGP) :	2.88
Log Po/w (XLOGP3) :	3.03
Log Po/w (WLOGP) :	3.42
Log Po/w (MLOGP) :	2.85
Log Po/w (SILICOS-IT) :	3.34
Consensus Log Po/w :	3.1

Druglikeness

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

Water Solubility

Log S (ESOL) :	-3.72
Solubility :	0.0707 mg/ml ; 0.00019 mol/l
Class :	Soluble
Log S (Ali) :	-4.48
Solubility :	0.0124 mg/ml ; 0.0000333 mol/l
Class :	Moderately soluble
Log S (SILICOS-IT) :	-5.78
Solubility :	0.000612 mg/ml ; 0.00000165 mol/l
Class :	Moderately soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	2.0
Synthetic accessibility :	3.47

Safety of [ 16881-33-7 ]

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:

Application In Synthesis of [ 16881-33-7 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

Upstream synthesis route of [ 16881-33-7 ]
Downstream synthetic route of [ 16881-33-7 ]

[ 16881-33-7 ] Synthesis Path-Upstream 1~5

1
[ 16881-33-7 ]
[ 16874-12-7 ]

Reference： [1] Journal of the American Chemical Society, 1960, vol. 82, p. 3359 - 3363

2
[ 16874-12-7 ]
[ 501-53-1 ]
[ 16881-33-7 ]

Reference： [1] Organic and Biomolecular Chemistry, 2005, vol. 3, # 20, p. 3805 - 3811
[2] Synlett, 2009, # 5, p. 720 - 723
[3] Patent: WO2005/97162, 2005, A2, . Location in patent: Page/Page column 539; 552-559

3
[ 507-19-7 ]
[ 1164-16-5 ]
[ 16881-33-7 ]

Reference： [1] Tetrahedron Letters, 1993, vol. 34, # 46, p. 7409 - 7412
[2] Tetrahedron, 2000, vol. 56, # 22, p. 3625 - 3633

4
[ 1164-16-5 ]
[ 115-11-7 ]
[ 16881-33-7 ]

Reference： [1] Journal of the American Chemical Society, 1960, vol. 82, p. 3359 - 3363

5
[ 16874-12-7 ]
[ 511244-40-9 ]
[ 67932-53-0 ]
[ 16881-33-7 ]

Reference： [1] Journal of Organic Chemistry, 2003, vol. 68, # 6, p. 2483 - 2486

[ 16881-33-7 ] Synthesis Path-Downstream 1~79

1
[ 16881-33-7 ]
[ 16874-12-7 ]

Reference： [1]Journal of the American Chemical Society,1960,vol. 82,p. 3359 - 3363

2
[ 1164-16-5 ]
[ 115-11-7 ]
[ 16881-33-7 ]

Reference： [1]Journal of the American Chemical Society,1960,vol. 82,p. 3359 - 3363

3
[ 507-19-7 ]
[ 1164-16-5 ]
[ 16881-33-7 ]

Reference： [1]Tetrahedron Letters,1993,vol. 34,p. 7409 - 7412
[2]Tetrahedron,2000,vol. 56,p. 3625 - 3633

4
[ 16881-33-7 ]
[ 77667-89-1 ]
[ 107932-35-4 ]
[ 107932-34-3 ]

Reference： [1]Synthesis,1986,vol. NO. 3,p. 209 - 211
[2]Synthesis,1986,vol. NO. 3,p. 209 - 211

5
[ 16881-33-7 ]
[ 77667-88-0 ]
[ 107932-35-4 ]

Reference： [1]Synthesis,1986,vol. NO. 3,p. 209 - 211

7
[ 16881-33-7 ]
[ 870456-12-5 ]

Reference： [1]Tetrahedron Letters,2000,vol. 41,p. 6893 - 6896
[2]Organic and Biomolecular Chemistry,2005,vol. 3,p. 3805 - 3811

8
[ 16881-33-7 ]
[ 464175-20-0 ]
[ 464175-21-1 ]

Reference： [1]Bioorganic Chemistry,2001,vol. 29,p. 357 - 379

9
[ 16874-12-7 ]
[ 511244-40-9 ]
[ 67932-53-0 ]
[ 16881-33-7 ]
5-nitro-7-nitrosoindoline [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2003,vol. 68,p. 2483 - 2486

10
[ 866993-70-6 ]
[ 16881-33-7 ]
[ 866993-72-8 ]

Reference： [1]Organic Letters,2005,vol. 7,p. 4531 - 4534

11
5-(7-bromo-3-chloro-1-methoxymethyl-2-oxo-2,3-dihydro-1H-indol-3-yl)-2-(1-tert-butoxycarbonylamino-2-methyl-propyl)-oxazole-4-carboxylic acid methyl ester [ No CAS ]
[ 16881-33-7 ]
5-{3-[4-((S)-2-benzyloxycarbonylamino-2-tert-butoxycarbonyl-ethyl)-phenoxy]-7-bromo-1-methoxymethyl-2-oxo-2,3-dihydro-1H-indol-3-yl}-2-((R)-1-tert-butoxycarbonylamino-2-methylpropyl)-oxazole-4-carboxylic acid methyl ester [ No CAS ]

Reference： [1]Organic Letters,2005,vol. 7,p. 4531 - 4534

12
[ 16874-12-7 ]
[ 501-53-1 ]
[ 16881-33-7 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydrogencarbonate; In tetrahydrofuran; water; at 0 - 20℃; for 27.0h;	Method UU Preparation of N-Benzyloxycarbonyl-L-Tyrosine tert-Butyl Ester To a 0C suspension of L-tyrosine tert-butyl ester (Bachem, 1.0 eq) and sodium bicarbonate (2.0 eq) in a 1:1 mixture of THF and water was added slowly with stirring benzyl chloroformate (1.1 eq). After the addition, the mixture was stirred at 0C for 3 h and at room temperature for 24 h. The mixture was diluted with diethyl ether, and the aqueous layer was separated. The organic extracts were washed with saturated sodium chloride, treated with anhydrous magnesium sulfate, filtered, and evaporated to afford N-benzyloxycarbonyl-L-tyrosine tert-butyl ester of sufficient purity for immediate conversion of the tyrosine hydroxyl into a carbamate.

Reference： [1]Organic and Biomolecular Chemistry,2005,vol. 3,p. 3805 - 3811
[2]Synlett,2009,p. 720 - 723
[3]Patent: WO2005/97162,2005,A2 .Location in patent: Page/Page column 539; 552-559

13
[ 358-23-6 ]
[ 16881-33-7 ]
[ 145205-85-2 ]

Yield	Reaction Conditions	Operation in experiment
		In the above formula, Tf is trifluoromethanesulfonyl. To an anhydrous dichloromethane solution (400 mL) of N-benzyloxycarbonyl-L-tyrosine t-butyl ester (81.3 g), anhydrous pyridine (88.5 mL, 1.09 M) was added, followed by cooling to 0 to 5C. Then, trifluoromethanesulfonic acid anhydride (43.0 mL, 262 mM) was added dropwise, followed by stirring at the same temperature for 2 hours. To the reaction solution, water (800 mL) and dichloromethane (1 L) were added, to be separated, and the organic layer was washed sequentially with a 0.5 N aqueous sodium hydroxide solution (650 mL), water (800 mL), 1N hydrochloric acid (2 x 1 L) and water (1 L). The organic layer was dried with anhydrous sodium sulfate, and concentrated, to obtain Compound 52 (105.9 g) as a milky white solid. Physicochemical property of Compound 52 Molecular weight: 503 ESI (LC/MS positive mode) 504 (M+H+) 1H-NMR Chemical shift value delta (in deuterated chloroform): 1.37 (9H, s), 3.10 (2H, d, J=6.5Hz), 4.52 (1H, dt, J=7.5, 6.5Hz), 5.07 (1H, d, J=12.5Hz), 5.12 (1H, d, J=12.5Hz), 5.30 (1H, d, J=7.5Hz), 7.16 (2H, d, J=9.0Hz), 7.23 (2H, d, J=9.0Hz), 7.30-7.43 (5H, m)

Reference： [1]Chemical and Pharmaceutical Bulletin,2001,vol. 49,p. 258 - 267
[2]Patent: EP1857456,2007,A1 .Location in patent: Page/Page column 65-66

14
[ 16881-33-7 ]
[ 79-44-7 ]
[ 1139879-63-2 ]

Yield	Reaction Conditions	Operation in experiment
	With dmap; triethylamine; In dichloromethane; at 37℃; for 16.0h;	Method VV Preparation of N Benzyloxycarbonyl-L-4-(N,N Dimethylcarbamyloxy)phenylalanine tert-Butyl Ester A mixture of N-benzyloxycarbonyl-L-tyrosine tert-butyl ester (1.0 eq), 4- dimethylaminopyridine (1.0 eq), triethylamine (1.5 eq), dimethylcarbamylchloride (1.2 eq), and dichloromethane was heated to 37C for 16 h. The mixture was diluted with additional dichloromethane and washed sequentially with 1.0 M potassium bisulfate, water, saturated sodium bicarbonate, and saturated sodium chloride. The organic extracts were treated with anhydrous magnesium sulfate, filtered, and evaporated to afford N-benzyloxycarbonyl-L-4-(N,N- dimethylcarbamyloxy) phenylalanine tert-butyl ester as a white solid of sufficient purity for immediate conversion to L-4-(N,N-dimethylcarbamyloxy)phenylalanine tert-butyl ester.

Reference： [1]Patent: WO2005/97162,2005,A2 .Location in patent: Page/Page column 539; 552-559

15
[ 16881-33-7 ]
[ 169158-08-1 ]

Reference： [1]Chemical and Pharmaceutical Bulletin,2001,vol. 49,p. 258 - 267

16
[ 16881-33-7 ]
[ 169158-07-0 ]

Reference： [1]Chemical and Pharmaceutical Bulletin,2001,vol. 49,p. 258 - 267

17
[ 16881-33-7 ]
4-[2-amino-3-(4-tert-butoxycarbonylmethyl-2-methoxycarbonylmethyl-3-oxo-piperazin-1-yl)-3-oxo-propyl]-benzoic acid methyl ester [ No CAS ]

Reference： [1]Chemical and Pharmaceutical Bulletin,2001,vol. 49,p. 258 - 267

18
[ 16881-33-7 ]
[ 169158-09-2 ]

Reference： [1]Chemical and Pharmaceutical Bulletin,2001,vol. 49,p. 258 - 267

19
[ 16881-33-7 ]
(S)-4-(4-Amidinobenzoyl-L-4-Methoxycarbonylphenylalanyl)-3-Methoxycarbonylmethyl-2-Oxopiperazine-1-Acetic Acid [ No CAS ]

Reference： [1]Chemical and Pharmaceutical Bulletin,2001,vol. 49,p. 258 - 267

20
[ 16881-33-7 ]
4-[3-(4-tert-butoxycarbonylmethyl-2-methoxycarbonylmethyl-3-oxo-piperazin-1-yl)-2-(4-carbamimidoyl-benzoylamino)-3-oxo-propyl]-benzoic acid methyl ester [ No CAS ]

Reference： [1]Chemical and Pharmaceutical Bulletin,2001,vol. 49,p. 258 - 267

21
[ 16881-33-7 ]
[ 870456-15-8 ]

Reference： [1]Organic and Biomolecular Chemistry,2005,vol. 3,p. 3805 - 3811

22
[ 16881-33-7 ]
[ 870456-14-7 ]

Reference： [1]Organic and Biomolecular Chemistry,2005,vol. 3,p. 3805 - 3811

23
[ 16881-33-7 ]
5-[2-(benzyloxycarbonyl)amino-2-tert-butoxycarbonyl]ethyl-3-formyl-3-phenyl-3-dihydrobenzo[b]furan-2-yl acetate [ No CAS ]

Reference： [1]Organic and Biomolecular Chemistry,2005,vol. 3,p. 3805 - 3811

24
[ 16881-33-7 ]
[ 870456-16-9 ]

Reference： [1]Organic and Biomolecular Chemistry,2005,vol. 3,p. 3805 - 3811

25
[ 16881-33-7 ]
[ 870456-13-6 ]

Reference： [1]Organic and Biomolecular Chemistry,2005,vol. 3,p. 3805 - 3811

26
[ 16881-33-7 ]
N-benzyloxycarbonyl-3-iodo-O-[2-(2-nitrophenyl)but-2-enoyl]tyrosine tert-butyl ester [ No CAS ]

Reference： [1]Organic and Biomolecular Chemistry,2005,vol. 3,p. 3805 - 3811

27
[ 16881-33-7 ]
3-[3-(3-allyl-7-bromo-2-oxo-2,3-dihydro-benzofuran-3-yl)-4-benzyloxy-phenyl]-2-benzyloxycarbonylamino-propionic acid tert-butyl ester [ No CAS ]

Reference： [1]Organic and Biomolecular Chemistry,2005,vol. 3,p. 3805 - 3811

28
[ 16881-33-7 ]
[ 302964-51-8 ]

Reference： [1]Organic and Biomolecular Chemistry,2005,vol. 3,p. 3805 - 3811
[2]Tetrahedron Letters,2000,vol. 41,p. 6893 - 6896

29
[ 16881-33-7 ]
[ 302964-52-9 ]

Reference： [1]Organic and Biomolecular Chemistry,2005,vol. 3,p. 3805 - 3811
[2]Tetrahedron Letters,2000,vol. 41,p. 6893 - 6896

30
[ 16881-33-7 ]
[ 302964-53-0 ]

Reference： [1]Organic and Biomolecular Chemistry,2005,vol. 3,p. 3805 - 3811
[2]Tetrahedron Letters,2000,vol. 41,p. 6893 - 6896

31
[ 16881-33-7 ]
[ 302964-54-1 ]

Reference： [1]Organic and Biomolecular Chemistry,2005,vol. 3,p. 3805 - 3811
[2]Tetrahedron Letters,2000,vol. 41,p. 6893 - 6896

32
[ 16881-33-7 ]
[ 302964-56-3 ]

Reference： [1]Organic and Biomolecular Chemistry,2005,vol. 3,p. 3805 - 3811
[2]Tetrahedron Letters,2000,vol. 41,p. 6893 - 6896

33
[ 16881-33-7 ]
[ 302964-50-7 ]

Reference： [1]Organic and Biomolecular Chemistry,2005,vol. 3,p. 3805 - 3811
[2]Tetrahedron Letters,2000,vol. 41,p. 6893 - 6896

34
[ 16881-33-7 ]
[ 302964-55-2 ]

Reference： [1]Organic and Biomolecular Chemistry,2005,vol. 3,p. 3805 - 3811
[2]Tetrahedron Letters,2000,vol. 41,p. 6893 - 6896

35
[ 16881-33-7 ]
5-{3-[5-((S)-2-benzyloxycarbonylamino-2-tert-butoxycarbonyl-ethyl)-2-hydroxyphenyl]-7-bromo-1-methoxymethyl-2-oxo-2,3-dihydro-1H-indol-3-yl}-2-((R)-1-tert-butoxycarbonylamino-2-methylpropyl)-oxazole-4-carboxylic acid methyl ester [ No CAS ]

Reference： [1]Organic Letters,2005,vol. 7,p. 4531 - 4534

36
[ 16881-33-7 ]
[ 627-18-9 ]
tert-butyl (2S)-3-[4-(3-hydroxypropoxy)phenyl]-2-[(phenylmethoxy)carbonylamino]propanoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
63%	With caesium carbonate; In N,N-dimethyl-formamide; at 20℃; for 24.0h;	1. tert-butyl (2S)-3-[4-(3-hydroxypropoxy)phenyl]-2-[(phenylmethoxy)carbonylamino]propanoate A mixture of <strong>[16881-33-7]N-(benzyloxycarbonyl)-L-tyrosine tert-butyl ester</strong> (0.37 g, 1.0 mmol), 3-bromo-1-propanol (0.09 ML, 1.0 mmol), and cesium carbonate (0.33 g, 1.0 mmol) in anhydrous N,N-dimethylformamide (5 ML) was stirred at room temperature for 24 h.. The reaction mixture was evaporated to dryness under high vacuum and the residue was partitioned between water and ethyl acetate.. The aqueous layer was separated and extracted with ethyl acetate.. The ethyl acetate extracts were combined and washed once with saturated sodium bicarbonate and brine.. The ethyl acetate was dried and evaporated to dryness.. The residue was purified on a silica gel column (10 g Waters Sep-Pak) by eluding with a gradient of ethyl acetate and hexane from 20:80 to 30:70.. The pure fractions were combined and evaporated to dryness to give the title compound (0.269 g, 63% yield) as a clear oil. 1H NMR (300 MHz, CDCl3) delta7.34 (m, 5H), 7.05 (d, J=8.6 Hz, 2H), 6.80 (m, 2H), 5.22 (d, J=8.1 Hz, 1H), 5.10 (d, J=2.8 Hz, 2H), 4.48 (q, J=8.1 Hz, 1H), 4.09 (t, J=6.0 Hz, 2H), 3.86 (t, J=6.0 Hz, 2H), 3.02 (m, 2H), 2.03 (p, J=6.0 Hz, 2H), 1.41 (s, 9H).

Reference： [1]Patent: US6344484,2002,B1 .Location in patent: Page column 24-25

37
[ 2969-81-5 ]
[ 16881-33-7 ]
[ 201402-17-7 ]

Yield	Reaction Conditions	Operation in experiment
9.4 g (97%)	With caesium carbonate; In acetone;	a tert-Butyl (2S)-2-Benzyloxycarbonylamino-3-(4-(3-ethoxycarbonylpropyloxy)phenyl)propionate 7.42 g (0.02 mol) of N-benzyloxycarbonyl-L-tyrosine tert-butyl ester were refluxed for 6 h together with 9.77 g(0.03 mol) of cesium carbonate and 3.9 g (0.02 mol) of ethyl 4-bromo-butyrate in about 60 ml of acetone. After cooling the reaction mixture, the solvent was removed in vacuo. The residue was partitioned between ethyl acetate and water (1/1). After separation of the phases, the organic phase was washed two times each with water and saturated sodium chloride solution, dried over sodium sulfate and concentrated in vacuo. The oily crude product was purified by flash chromatography on silica gel (dichloromethane/acetonitrile 25/1). Yield: 9.4 g (97%) of viscous oil. Rf=0.36 (silica gel, dichloromethane/methanol 9911).

Reference： [1]Patent: US6492356,2002,B1

38
[ 5292-43-3 ]
[ 16881-33-7 ]
[ 179187-86-1 ]

Yield	Reaction Conditions	Operation in experiment
		f N-Benzyloxycarbonyl-3-[4-(tert-butoxycarbonylmethoxy)-phenyl]-alanine-tert-butyl ester 5.57 g (15 mmol) of N-benzyloxycarbonyl-tyrosine-tert-butyl ester is reacted with bromoacetic acid-tert-butyl ester to alkylated phenol analogously to Example 1a). Yield: 6.1 g (83.7% of theory) of colorless oil.

Reference： [1]Patent: US5885548,1999,A

39
[ 54149-17-6 ]
[ 16881-33-7 ]
[ 179187-74-7 ]

Yield	Reaction Conditions	Operation in experiment
		f N-Benzyloxycarbonyl-3-[4-(1,4,7-trioxaoctyl)-phenyl]-alanine-tert-butyl ester 7.43 g (20 mmol) of N-benzyloxycarbonyl-tyrosine-tert-butyl ester is reacted with 1-bromo-2-(2-methoxyethoxy)-ethane to alkylated phenol analogously to Example a). Yield: 8.2 g (86.6% of theory) of colorless oil.

Reference： [1]Patent: US5885548,1999,A

40
[ 16881-33-7 ]
[ 100-39-0 ]
[ 142196-39-2 ]

Reference： [1]Synlett,2009,p. 720 - 723

41
[ 37595-74-7 ]
[ 16881-33-7 ]
(S)-tert-butyl 2-(((benzyloxy)carbonyl)amino)-3-(4-(((trifluoromethyl)sulfonyl)oxy)-phenyl)propanoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
79%	With magnesium sulfate; N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20℃;	Prepared using General Procedure 9: A stirred solution of <strong>[16881-33-7]<strong>[16881-33-7](S)-tert-butyl 2-(((benzyloxy)carbonyl)amino)-3-(4-hydroxyphenyl)propanoate</strong> hydrate</strong> (25 g, 64.2 mmol) in DCM (100 mL) was treated with magnesium sulfate (4.01 g, 33.7 mmol). After 15 min, the mixture was filtered and washed with DCM (2 x 20 mL). The organics were treated with N-ethyl-N-isopropylpropan-2-amine (17.41 g, 134.7 mmol) and stirred. This solution was treated with 1,1,1-trifluoro-N-phenyl-N- ((trifluoromethyl)sulfonyl)methanesulfonamide (26.44 g, 74.01 mmol) and the mixture was allowed to stir overnight at RT. The mixture was treated with water (50 mL) and saturated aqueous NaHC03 (20 mL) and stirred vigorously for 10 min. The layers were separated and the organic layer was further washed with saturated aqueous NaHC03 (2 x 50 mL), water (50 mL), and saturated aqueous NaHC03 (50 mL) and concentrated. The compound was purified by chromatography (EA / hexanes) to afford 26.85 g (79%) of {S)-tert- vXy 2-(((benzyloxy)carbonyl)amino)-3-(4- (((trifluoromethyl)sulfonyl)oxy)phenyl) propanoate INT-5. LCMS-ESI (m/z) calculated for C22H24F3NO7S: 503.1; found 526.1 [M + Na]+, = 4.12 min (Method 3).

Reference： [1]Patent: WO2013/90454,2013,A2 .Location in patent: Paragraph 00296

42
[ 23877-12-5 ]
[ 16881-33-7 ]
[ 1427753-32-9 ]

Yield	Reaction Conditions	Operation in experiment
1.21 g	With potassium carbonate; In N,N-dimethyl-formamide; at 90℃;	Preparation Example 59 To a solution of <strong>[16881-33-7]tert-butyl N-[(benzyloxy)carbonyl]-L-tyrosinate</strong> (1.00 g) in N,N-dimethylformamide (10.0 mL) were added potassium carbonate (2.71 g) and tert-butyl 2-bromo-2-methylpropanoate (2.01 mL), followed by stirring at 90C overnight. To the reaction suspension was added water, followed by extraction with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane-ethyl acetate) to obtain tert-butyl N-[(benzyloxy)carbonyl]-4-(1-tert-butoxy-2-methyl-1-oxopropan-2-yl)-L-tyrosinate (1.21 g).

Reference： [1]Patent: EP2757093,2014,A1 .Location in patent: Paragraph 0192

43
[ 16881-33-7 ]
[ 1443792-06-0 ]

Reference： [1]Patent: WO2014/201172,2014,A1
[2]Patent: WO2016/15014,2016,A1

44
[ 16881-33-7 ]
[ 1443792-07-1 ]

Reference： [1]Patent: WO2014/201172,2014,A1
[2]Patent: WO2016/15014,2016,A1

45
[ 16881-33-7 ]
[ 1443792-08-2 ]

Reference： [1]Patent: WO2014/201172,2014,A1

46
[ 16881-33-7 ]
[ 1443792-09-3 ]

Reference： [1]Patent: WO2014/201172,2014,A1

47
[ 16881-33-7 ]
C₄₁H₅₁N₃O₄ [ No CAS ]

Reference： [1]Patent: WO2014/201172,2014,A1

48
[ 16881-33-7 ]
[ 1443789-07-8 ]

Reference： [1]Patent: WO2014/201172,2014,A1

49
[ 16881-33-7 ]
[ 1443792-10-6 ]

Reference： [1]Patent: WO2014/201172,2014,A1

50
[ 16881-33-7 ]
[ 1443792-11-7 ]

Reference： [1]Patent: WO2014/201172,2014,A1

51
[ 16881-33-7 ]
C₃₉H₄₉N₃O₄S [ No CAS ]

Reference： [1]Patent: WO2014/201172,2014,A1

52
[ 16881-33-7 ]
[ 1443789-98-7 ]

Reference： [1]Patent: WO2014/201172,2014,A1

53
[ 16881-33-7 ]
[ 1443791-00-1 ]

Reference： [1]Patent: WO2014/201172,2014,A1

54
[ 16881-33-7 ]
C₄₄H₅₇N₅O₆S [ No CAS ]

Reference： [1]Patent: WO2014/201172,2014,A1

55
[ 37595-74-7 ]
[ 16881-33-7 ]
[ 145205-85-2 ]

Yield	Reaction Conditions	Operation in experiment
79%		General procedure: (General Procedure 9: Formation of Trflate.[00420j A solution of the phenol (1.0 eq) in DCM (0.25 M) was treated with 1,1- trifluoro-N-phenyl-N-((trifluoromethyl)sulfonyl)methanesulfonamide (1 .1 eq). The reaction mixture was stirred at room temperature until complete. The reaction was stirred with water and saturated aqueous NaHCO3. The organic layers was dried and concentrated. The material was purified by chromatography or alternatively used without purification.S)-tert-butyl 2-(((benzyloxy)carbonyl)amino)-3- (4-(((trijluoromethyl)sulfonyl)oxy)- phenyl) propanoate (INT-5) [00491j Prepared using General Procedure 9: A stirred solution of (S)-tert-butyl 2- (((benzyloxy)carbonyl)amino)-3 -(4-hydroxyphenyl)propanoate hydrate (25 g, 64.2 mmol) in DCM (100 mL) was treated with MgSO4 (4.01 g, 33.7 mmol). After 15 mm, the mixture was filtered and washed with DCM (2 x 20 mL). The organics were treated with N-ethyl-N-isopropylpropan-2-amine (17.41 g, 134.7 mmol) and stirred. Thissolution was treated with 1,1,1 -trifluoro-N-phenyl-N((trifluoromethyl)sulfonyl)methanesulfonamide (26.44 g, 74.01 mmol) and the mixture was allowed to stir overnight at room temperature. The mixture was treated with water (50 mL) and saturated aqueous NaHCO3 (20 mL) and stirred vigorously for 10 mm. The layers were separated and the organic layer was further washed with saturated aqueous NaHCO3 (2 x 50 mL), water (50 mL), and saturated aqueous NaHCO3 (50 mL) and concentrated. The compound was purified by chromatography (EA / hexanes) to afford 26.85 g (79%) of (S)-tert-butyl 2-(((benzyloxy)carbonyl)amino)-3 -(4- (((trifluoromethyl)sulfonyl)oxy)phenyl) propanoate INT-5. LCMS-ESI (mlz) calculated for C22H24F3N07S: 503.1; found 526.1 [M + Na], tR = 4.12 mm (Method 3).
79%		Prepared using General Procedure 9: A stirred solution of <strong>[16881-33-7]<strong>[16881-33-7](S)-tert-butyl 2-(((benzyloxy)carbonyl)amino)-3-(4-hydroxyphenyl)propanoate</strong> hydrate</strong> (25 g, 64.2 mmol) in DCM (100 mL) was treated with MgSO4 (4.01 g, 33.7 mmol). After 15 min, the mixture was filtered and washed with DCM (2 x 20 mL). The organics were treated with N-ethyl-N-isopropylpropan-2-amine (17.41 g, 134.7 mmol) and stirred. This solution was treated with 1,1,1-trifluoro-N-phenyl-N- ((trifluoromethyl)sulfonyl)methanesulfonamide (26.44 g, 74.01 mmol) and the mixture was allowed to stir overnight at room temperature.The mixture was treated with water (50 mL) and saturated aqueous NaHCO3 (20 mL) and stirred vigorously for 10 min. The layers were separated and the organic layer was further washed with saturated aqueous NaHCO3 (2 x 50 mL), water (50 mL), and saturated aqueous NaHCO3 (50 mL) and concentrated. The compound was purified by chromatography (EA / hexanes) to afford 26.85 g (79%) of (S)-tert-butyl 2-(((benzyloxy)carbonyl)amino)-3-(4- (((trifluoromethyl)sulfonyl)oxy)phenyl) propanoate INT-5. LCMS-ESI (m/z) calculated for C22H24F3NO7S: 503.1; found 526.1 [M + Na]+, tR = 4.12 min (Method 3).

Reference： [1]Patent: WO2014/201172,2014,A1 .Location in patent: Paragraph 00420; 00491
[2]Patent: WO2016/15014,2016,A1 .Location in patent: Paragraph 0269

56
[ 16881-33-7 ]
5-(tert-butyl)-N-((S)-3-(4-(5-((1RS,1'r,4'RS)-4'-ethyl-[1,1'-bi(cyclohexan)]-3-en-4-yl)pyrimidin-2-yl)phenyl)-1-(methylsulfonamido)-1-oxopropan-2-yl)thiophene-2-carboxamide [ No CAS ]