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Chemical Structure| 171663-13-1 Chemical Structure| 171663-13-1
Chemical Structure| 171663-13-1

tert-Butyl 3-bromobenzylcarbamate

CAS No.: 171663-13-1

4.5 *For Research Use Only !

Cat. No.: A134949 Purity: 95%

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Product Citations

Product Citations

Guo, Sheng ; Wu, Yifan ; Luo, Shao-Xiong Lennon ; Swager, Timothy M. ;

Abstract: Heterogenous catalysts with confined nanoporous catalytic sites are shown to have high activity and size selectivity. A solution-processable nanoporous organic polymer (1-BPy-Pd) catalyst displays high catalytic performance (TON > 200K) in the heterogeneous Suzuki–Miyaura coupling (SMC) reaction and can be used for the preparation of the intermediates in the synthesis of pharmaceutical agents. In comparison to the homogeneous catalyst analogue (2,2′-BPy)PdCl2, the heterogenous system offers size-dependent catalytic activity when bulkier substrates are used. Furthermore, the catalyst can be used to create catalytic impellers that simplify its use and recovery. We found that this system also works for applications in heterogenous Heck and nitroarenes reduction reactions. The metal-binding nanoporous polymer reported here represents a versatile platform for size-selective heterogeneous and recyclable catalysts.

Keywords: nanoporous organic polymer ; heterogeneous catalyst ; Suzuki−Miyaura coupling reaction ; size-selective reaction ; catalyst processing

Alternative Products

Product Details of [ 171663-13-1 ]

CAS No. :171663-13-1
Formula : C12H16BrNO2
M.W : 286.17
SMILES Code : O=C(OC(C)(C)C)NCC1=CC=CC(Br)=C1
MDL No. :MFCD08703139
InChI Key :BSEVOUCZQOLENZ-UHFFFAOYSA-N
Pubchem ID :11033439

Safety of [ 171663-13-1 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302
Precautionary Statements:P280-P305+P351+P338

Calculated chemistry of [ 171663-13-1 ] Show Less

Physicochemical Properties

Num. heavy atoms 16
Num. arom. heavy atoms 6
Fraction Csp3 0.42
Num. rotatable bonds 5
Num. H-bond acceptors 2.0
Num. H-bond donors 1.0
Molar Refractivity 67.66
TPSA ?

Topological Polar Surface Area: Calculated from
Ertl P. et al. 2000 J. Med. Chem.

38.33 Ų

Lipophilicity

Log Po/w (iLOGP)?

iLOGP: in-house physics-based method implemented from
Daina A et al. 2014 J. Chem. Inf. Model.

2.77
Log Po/w (XLOGP3)?

XLOGP3: Atomistic and knowledge-based method calculated by
XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry

3.11
Log Po/w (WLOGP)?

WLOGP: Atomistic method implemented from
Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.

3.32
Log Po/w (MLOGP)?

MLOGP: Topological method implemented from
Moriguchi I. et al. 1992 Chem. Pharm. Bull.
Moriguchi I. et al. 1994 Chem. Pharm. Bull.
Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.

3.06
Log Po/w (SILICOS-IT)?

SILICOS-IT: Hybrid fragmental/topological method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

2.73
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

3.0

Water Solubility

Log S (ESOL):?

ESOL: Topological method implemented from
Delaney JS. 2004 J. Chem. Inf. Model.

-3.52
Solubility 0.0862 mg/ml ; 0.000301 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-3.58
Solubility 0.0747 mg/ml ; 0.000261 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble
Log S (SILICOS-IT)?

SILICOS-IT: Fragmental method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

-4.6
Solubility 0.00719 mg/ml ; 0.0000251 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Moderately soluble

Pharmacokinetics

GI absorption?

Gatrointestinal absorption: according to the white of the BOILED-Egg

High
BBB permeant?

BBB permeation: according to the yolk of the BOILED-Egg

Yes
P-gp substrate?

P-glycoprotein substrate: SVM model built on 1033 molecules (training set)
and tested on 415 molecules (test set)
10-fold CV: ACC=0.72 / AUC=0.77
External: ACC=0.88 / AUC=0.94

No
CYP1A2 inhibitor?

Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.83 / AUC=0.90
External: ACC=0.84 / AUC=0.91

Yes
CYP2C19 inhibitor?

Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.80 / AUC=0.86
External: ACC=0.80 / AUC=0.87

Yes
CYP2C9 inhibitor?

Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set)
and tested on 2075 molecules (test set)
10-fold CV: ACC=0.78 / AUC=0.85
External: ACC=0.71 / AUC=0.81

Yes
CYP2D6 inhibitor?

Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set)
and tested on 1068 molecules (test set)
10-fold CV: ACC=0.79 / AUC=0.85
External: ACC=0.81 / AUC=0.87

No
CYP3A4 inhibitor?

Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set)
and tested on 2579 molecules (test set)
10-fold CV: ACC=0.77 / AUC=0.85
External: ACC=0.78 / AUC=0.86

No
Log Kp (skin permeation)?

Skin permeation: QSPR model implemented from
Potts RO and Guy RH. 1992 Pharm. Res.

-5.84 cm/s

Druglikeness

Lipinski?

Lipinski (Pfizer) filter: implemented from
Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev.
MW ≤ 500
MLOGP ≤ 4.15
N or O ≤ 10
NH or OH ≤ 5

0.0
Ghose?

Ghose filter: implemented from
Ghose AK. et al. 1999 J. Comb. Chem.
160 ≤ MW ≤ 480
-0.4 ≤ WLOGP ≤ 5.6
40 ≤ MR ≤ 130
20 ≤ atoms ≤ 70

None
Veber?

Veber (GSK) filter: implemented from
Veber DF. et al. 2002 J. Med. Chem.
Rotatable bonds ≤ 10
TPSA ≤ 140

0.0
Egan?

Egan (Pharmacia) filter: implemented from
Egan WJ. et al. 2000 J. Med. Chem.
WLOGP ≤ 5.88
TPSA ≤ 131.6

0.0
Muegge?

Muegge (Bayer) filter: implemented from
Muegge I. et al. 2001 J. Med. Chem.
200 ≤ MW ≤ 600
-2 ≤ XLOGP ≤ 5
TPSA ≤ 150
Num. rings ≤ 7
Num. carbon > 4
Num. heteroatoms > 1
Num. rotatable bonds ≤ 15
H-bond acc. ≤ 10
H-bond don. ≤ 5

0.0
Bioavailability Score?

Abbott Bioavailability Score: Probability of F > 10% in rat
implemented from
Martin YC. 2005 J. Med. Chem.

0.55

Medicinal Chemistry

PAINS?

Pan Assay Interference Structures: implemented from
Baell JB. & Holloway GA. 2010 J. Med. Chem.

0.0 alert
Brenk?

Structural Alert: implemented from
Brenk R. et al. 2008 ChemMedChem

0.0 alert: heavy_metal
Leadlikeness?

Leadlikeness: implemented from
Teague SJ. 1999 Angew. Chem. Int. Ed.
250 ≤ MW ≤ 350
XLOGP ≤ 3.5
Num. rotatable bonds ≤ 7

No; 1 violation:MW<0.0
Synthetic accessibility?

Synthetic accessibility score: from 1 (very easy) to 10 (very difficult)
based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties,
trained on 12'782'590 molecules and tested on 40 external molecules (r2 = 0.94)

1.96

Application In Synthesis of [ 171663-13-1 ]

* 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.

  • Downstream synthetic route of [ 171663-13-1 ]

[ 171663-13-1 ] Synthesis Path-Downstream   1~28

  • 1
  • [ 144104-59-6 ]
  • [ 171663-13-1 ]
  • [3-(1H-Indol-5-yl)-benzyl]-carbamic acid tert-butyl ester [ No CAS ]
  • 2
  • [ 147621-18-9 ]
  • [ 171663-13-1 ]
  • [3-(1H-Indol-6-yl)-benzyl]-carbamic acid tert-butyl ester [ No CAS ]
  • 3
  • [ 210889-31-9 ]
  • [ 171663-13-1 ]
  • [3-(1H-Indol-7-yl)-benzyl]-carbamic acid tert-butyl ester [ No CAS ]
  • 4
  • [ 171663-13-1 ]
  • 2-benzenesulfonylamino-3-[(5-bromo-thiophene-2-carbonyl)-amino]-propionic acid <i>tert</i>-butyl ester [ No CAS ]
  • [ 603126-93-8 ]
  • 5
  • [ 171663-13-1 ]
  • 3-[(5-bromo-thiophene-2-carbonyl)-amino]-2-(2,4,6-trimethyl-benzenesulfonylamino)-propionic acid <i>tert</i>-butyl ester [ No CAS ]
  • 3-({5-[3-(<i>tert</i>-butoxycarbonylamino-methyl)-phenyl]-thiophene-2-carbonyl}-amino)-2-(2,4,6-trimethyl-benzenesulfonylamino)-propionic acid <i>tert</i>-butyl ester [ No CAS ]
  • 6
  • [ 73183-34-3 ]
  • [ 171663-13-1 ]
  • [ 832114-05-3 ]
YieldReaction ConditionsOperation in experiment
86.5% With potassium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,4-dioxane; at 80℃; Bis(pinacolato) diboron (588mg, 2.0 mmol), reactant (286 mg, 1.0 mmol), potassium carbonate (276 mg, 2.0 mmol) and PdC12(dppf)CH2Cl2 (25 mg, 0.03 mmol) were added to a reaction flask which was purged thoroughly with N2. 10ml of dried dioxane was added via syringe and the reaction was heated to 80 0C for overnight. After LC-MS showed the reaction was complete, the solution was then cooled to room temperature and filtered and concentrated. Purification by chromatography (0-10% EtOAc: hexane), giving 288 mg of product as a white solid, yield: 86.5%. m/z 334 (M+H+).
83% With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate; In dimethyl sulfoxide; at 80℃; for 4h;Inert atmosphere; In the three-neck flask was added Intermediate j (10mmol),Pinacol diborate (2.67g, 10.5mmol),Potassium acetate (2.9g, 30mmol), [1,1'-bis(diphenylphosphine)ferrocene]palladium dichloromethane complex (245mg, 0.3mmol), protected by nitrogen, Add 15mL of dimethyl sulfoxide, and react at 80 C for 4 hours. Water was added after cooling, extraction with ethyl acetate, washing with saturated brine, and drying with anhydrous sodium sulfate. Column chromatography was used to obtain 2.76 g of intermediate k as a white solid
  • 8
  • [ 171663-13-1 ]
  • 3-[5-(3-aminomethyl-phenyl)-thiophene-2-carbonyl]-amino}-2-(2,4,6-trimethyl-benzenesulfonylamino)-propionic acid <i>tert</i>-butyl ester [ No CAS ]
  • 10
  • [ 171663-13-1 ]
  • (S)-2-Benzenesulfonylamino-3-[5-(3-guanidinomethyl-phenyl)-thiophene-2-carbonyl]-amino}-propionic acid; compound with trifluoro-acetic acid [ No CAS ]
  • 11
  • [ 24424-99-5 ]
  • [ 39959-54-1 ]
  • [ 171663-13-1 ]
YieldReaction ConditionsOperation in experiment
100% With triethylamine; In dichloromethane; at 20℃; for 16h; Example 19Synthesis of (E)-3-{3'-[(benzoylmethylamino)methyl]-2-butoxybiphenyl-4-yl}-2-methylacrylic acid a-tert-Butyl (3-bromobenzyl)carbamateA solution of 25 g (110 mmol) of 3-bromobenzylamine hydrochloride and 24.5 g (110 mmol) of tert-butyl dicarbonate in 250 mL of dichloromethane in the presence of 15.6 mL (110 mmol) of triethylamine is stirred at room temperature for 16 hours. The reaction medium is washed with water, the phases are separated by settling and the organic phase is dried over sodium sulfate. The solvent is evaporated off and 32.4 g (100%) of tert-butyl (3-bromobenzyl)carbamate are obtained in the form of crystals.
100% In dichloromethane; at 20℃; for 16h; A solution of 25.0 g (0.11 mol, 1 eq.) of 3-bromobenzylamine hydrochloride and of 24.52 g (0.11 mol, 1 eq.) of di(tert-butyl) dicarbonate in 250 ml of dichloromethane in the presence of 15.6 ml (0.11 mol, 1 eq.) of triethylamine is stirred at ambient temperature for 16 hours. The reaction medium is washedwith water and separated by settling, and the organic phase is dried over sodium sulphate. The solvent is evaporated and 32.41 g of tert-butyl (3-bromobenzyl)carbamate are obtained in the form of crystals. Yield = 100%
100% With triethylamine; In dichloromethane; at 20℃; To 224 3-bromobenzylamine hydrochloride (1.0 g, 4.5 mmol) and 212 di-tert-butyl dicarbonate (0.98g, 4.5 mmol) were added 12 dichloromethane (10 mL) and 14 triethylamine (0.63 mL, 4.5 mmol), andthe mixture was stirred at room temperature overnight. To the reaction mixture was added 52 water andthe mixture was extracted with dichloromethane. The organic layer was dried over sodium sulfate, thedesiccant was filtered off, and the solvent was evaporated to give the 225 title compound ( 1.3 g , 4.5mmol, 100%). MS(ESI) m/z 286 (M+H)+
100% With triethylamine; In dichloromethane; at 20℃; To a solution of (3-bromophenyl)methanamine hydrochloride (5.0 g, 23 mmol) and di-fer/-butyl dicarbonate (5.0 g, 24 mmol) in DCM (50 mL) was added triethylamine (3.2 mL, 23 mmol). The reaction was stirred overnight at room temperature. The mixture was washed with H20, and the organic layer was dried Na2S04), filtered, and concentrated to afford Intermediate 19A (6.5 g, quant.). lH NMR (CDC13): delta 7.43 (br s, 1H), 7.41-4.38 (m, 1H), 7.21-7.17 (m, 2H), 4.88 (br s, 1H), 4.30-4.29 (m, 2H), 1.47 (s, 9H).
90% With triethylamine; In methanol; at 20℃; Example 1.1.79: 3-(aminomethyl)benzonitrile; To (3-bromophenyl)methanamine hydrochloride (Aldrich, 4.0 g, 17.97 mmol) in MeOH (35 ml) , triethylamine (5.45 g, 53.91 mmol) was added followed by (Boc)2O (4.7 g, 21.6 mmol). Reaction mixture was stirred overnight at RT and the volatiles are removed on a rotavap under reduced pressure. Then the crude residue was column chromatographed (10% Ethyl acetate/Hexanes) to yield tert-butyl 3-bromobenzylcarbamate in 90% yield.
88% With triethylamine; In dichloromethane; at 20℃; for 18h; 40 g (183 mmol) of di-tert-butyl dicarbonate are added portionwise, at room temperature, to a mixture of 40.7 g (183 mmol) of 3-bromobenzylamine hydrochloride, 26 ml of triethylamine (183 mmol) and 450 ml of dichloromethane. After stirring for 18 hours, the reaction medium is poured into ice-cold water and extracted with dichloromethane. The organic phase is separated out by settling of the phases, dried over magnesium sulphate and evaporated. 46 g of tert-butyl (3-bromobenzyl) carbamate are obtained in a yield of 88%
88% With triethylamine; In dichloromethane; at 20℃; for 18h; 40 g (183 mmol) of di-tert-butyl dicarbonate are added portionwise, at room temperature, to a mixture of 40.7 g (183 mmol) of 3-bromobenzylamine hydrochloride, 26 ml of triethylamine (183 mmol) and 450 ml of dichloromethane. After stirring for 18 hours, the reaction medium is poured into ice-cold water and extracted with dichloromethane. The organic phase is separated out after settling of the phases, dried over magnesium sulphate and evaporated. 46 g of tert-butyl (3-bromobenzyl) carbamate are obtained in a yield of 88%.
86% With sodium hydrogencarbonate; In ethanol; at 20℃; Step a) (3-Bromo-benzyl)-carbamic acid tert-butyl ester (A-25a); 3-Bromo-benzyl amine hydrochloride( 3g, 13,5 mmol) and NaHCO3 (2.3g, 27 mmol) were mixed in ethanol (20 ml). BoC2O (4.4 g, 20.3 mmol) was added and the resulting reaction mixture stirred at room temperature over night. The solvent was evaporated under vacuum and the residue dissolved in EtOAc. The mixture was washed with brine, dried (Na2SOs), filtered and concentrated in vacuo. The crude product was purified by chromatography on a silica column (EtOAc in hexane 1 :10), which gave the title compound (3.3 g, 86%). LCMS m/z 287.22 (M+H)+
76% To a stirred solution of (3- bromophenyl)methanamine hydrochloride (2.0 g, 0.089 mol) in dichloromethane was added triethylamine (1.39 mL, 0.010 mol) and stirred for 10 minutes. After 10 minutes Di-tert- butyldi carbonate (2.35 g, 0.010 mol) was added and stirred for 6h. The reaction mixture was diluted with water and extracted in to dichloromethane. The combined organic layer was washed with water (10 mL), brine (10 mL), dried over anhydrous sodium sulfate and evaporated under reduced pressure. The crude product was purified by combiflash purifier with 18 % ethyl acetate in hexane as an eluent give the title compound as semi solid m/z = 187.9 [M + H]+; Yield: (2.2 g, 76 %).
With triethylamine; In dichloromethane; (a) tert-butyl (3-bromobenzyl)carbamate 40.7 g (183 mmol) of 3-bromobenzylamine hydrochloride, 26 ml of triethylamine (183 mmol) and 450 ml of dichloromethane are introduced into a round-bottomed flask and under a nitrogen stream. 40 g (183 mmol) of di-tert-butyl dicarbonate are added in small quantities at room temperature and the mixture is stirred overnight. The reaction medium is poured into ice-cold water, extracted with dichloromethane, the organic phase decanted off, dried over magnesium sulphate and evaporated off. 46 g (88%) of the expected product are recovered.
With triethylamine; In dichloromethane; (a) tert-Butyl (3-bromo benzyl)carbamate 15 g (67 mmol) of 3-bromobenzylaminehydrochloride, 9.4 ml of triethylamine (67 mmol) and 150 ml of dichloromethane are introduced into a round-bottomed flask under a stream of nitrogen. 15.5 ml (67 mmol) of di-tert-butyl dicarbonate are added portionwise at room temperature and the mixture is stirred for three hours. The reaction medium is poured into ice-cold water and extracted with dichloromethane, and the organic phase is separated out after settling of the phases has taken place, dried over magnesium sulfate and evaporated. 19.3 g (100%) of the expected product are collected.
Preparation 11: tert-Butyl (3-bromobenzyl)carbamate; Triethylamine (6.57L; 46.7 mol) was added to 3-bromobenzylamine hydrochloride (9.9 Kg; 44.5 mol) in ethyl acetate (39.6 L) and the resulting mixture was stirred for 30 minutes at 20 to 25C and was then cooled to 0C. A solution of di-ferf-butyl dicarbonate (10.7 Kg; 49 mol) in ethyl acetate (19.8L) was then added over 30 minutes at such a rate as to maintain the temperature between 0C and 20C. The reaction mixture was then stirred at 20 to 25C for 2 hours, water (29.7 L) was then added and the mixture was stirred vigorously for 10 minutes and then the phases were separated. The ethyl acetate phase was distilled and replaced with heptane under reduced pressure at 35 to 45C to a final volume of approximately 4OL and then the solution was cooled to 00C over 2 hours. The resulting suspension was stirred at O0C for 12 hours, then the product was collected by filtration, washing with heptane (2 x 3.37L) to provide the title compound as a white solid (10.26 Kg).1H NMR (400MHz, CDCI3) delta: 1.46 (s, 9H), 4.25-4.32 (m, 2H), 4.75-4.90 (bs, 1H), 7.16-7.22 (m, 2H), 7.39 (dt, 1H), 7.43 (bs, 1H) ppm.

  • 12
  • [ 171663-13-1 ]
  • [ 74-88-4 ]
  • [ 317358-61-5 ]
YieldReaction ConditionsOperation in experiment
100% b-tert-Butyl (3-bromobenzyl)methylcarbamate5.4 g (134 mmol) of 60% sodium hydride are added to a solution of 32 g (111 mmol) of <strong>[171663-13-1]tert-butyl (3-bromobenzyl)carbamate</strong> in 450 mL of dimethylformamide. The reaction medium is stirred at room temperature for 30 minutes and 21 mL (335 mmol) of iodomethane are then added. The reaction medium is stirred at room temperature for 20 hours and then hydrolyzed in water and extracted with ethyl acetate. The organic phases are combined, washed with saturated sodium chloride solution and dried over sodium sulfate. The solvent is evaporated off and 36.2 g (100%) of tert-butyl (3-bromobenzyl)methylcarbamate are obtained in the form of an orange-colored oil.
100% 5.4 g (0.134 mol, 1.2 eq.) of 60% sodium hydride are added to a solution of 32.0 g (0.111 mol, 1 eq.) of <strong>[171663-13-1]tert-butyl (3-bromobenzyl)carbamate</strong> in 450 ml of dimethylformamide. The reaction medium is stirred at ambient temperature for 30 minutes and then 20.9 ml (0.335 mol, 3 eq.) of iodomethane are added. The reaction medium is stirred at ambient temperature for 20 hours, then hydrolysed in water and extracted with ethyl acetate. The organic phases are combined, washed with a saturated sodium chloride solution and dried over sodium sulphate. The solvent is evaporated and 36.23 g of tert-butyl (3-bromobenzyl)(methyl)carbamate are obtained in the form of an orange oil. Yield = 100%
92% With sodium hydride; In DMF (N,N-dimethyl-formamide); 19 g (475 mmol) of sodium hydride (60% in oil) are added portionwise to a solution of 128 g (447 mmol) of tert-butyl (3-bromobenzyl) carbamate in 800 ml of DMF, and the reaction medium is stirred until the evolution of gas has ceased. 29.3 ml (470 mmol) of methyl iodide are added dropwise and stirring is continued for 18 hours. The reaction medium is poured into ice-cold water and extracted with ethyl acetate. The organic phase is separated out by settling of the phases, dried over magnesium sulphate and evaporated. 152.5 g of ter-butyl (3-bromobenzyl) -N-methylcarbamate are obtained in a yield of 92%
In N,N-dimethyl-formamide; (b) tert-butyl (3-bromobenzyl)-N-methylcarbamate 128 g (447 mmol) of <strong>[171663-13-1]tert-butyl (3-bromobenzyl)carbamate</strong> and 800 ml of DMF are introduced into a round-bottomed flask and under a nitrogen stream. 19 g (475 mmol) of sodium hydride (60% in oil) are added in small quantities and the mixture is stirred until the gas emission ceases. 29.3 ml (470 mmol) of methyl iodide are then added and the mixture is stirred overnight. The reaction medium is poured into ice-cold water, extracted with ethyl acetate, the organic phase decanted off, dried over magnesium sulphate and evaporated off. 152.5 g (92%) of the expected product are recovered.

  • 13
  • [ 24424-99-5 ]
  • [ 10269-01-9 ]
  • [ 171663-13-1 ]
YieldReaction ConditionsOperation in experiment
100% With sodium hydroxide; In tetrahydrofuran; water; at 20℃; for 0.5h; Sodium hydroxide (8.76 g, 219.0 mmol, 2.2 EQ.), di-tert-butyl dicarbonate (26.07 g, 119.45 MMOL, 1.2 EQ. ) AND WATER (100 ML) WERE ADDED TO A STIRRING SOLUTION OF 3-BROMOBENZYLAMINE (22.11 G, 99.55 MMOL, 1.0 EQ. ) IN TETRAHYDROFURAN (75 ML) OVER 30 minutes at room temperature. The mixture was extracted with dichloromethane and water twice. The organic phase was dried and concentrataed to give ter-butyl (3-BROMOBENZYL) -CARBAMATE (34.88G, 100%). LCMS: CALCD 286; OBSD (M+23) 309).
100% With sodium hydrogencarbonate; In tetrahydrofuran; at 20℃; for 3h; A 100-mL round-bottomed flask, equipped with magnetic stirring bar, was charged with THF (10 mL) and (3-bromophenyl) methanamine (1.86 g, 10 mmol) and sodium bicarbonate (1.68 g, 20 mmol), the di-tert-butyl dicarbonate (2.4 g, 11 mmol) was added. The resulted solution was stirred at room temperature for 3 h. The reaction mixture was filtered and the solvents are then removed under reduced pressure, the residue was pure enough for next step without further purification (2.86 g, yield: 100%). m/z 286 (MH-H+).
99% In dichloromethane; at 20℃; for 15h; To a solution of commercially available 3-bromo-benzylamine (938 mg) in dry dichloromethane (10 mL) was added added di-tert-butyl dicarbonate (1.10 g). The resulting clear solution was stirred at room temperature for 15 h and then concentrated to afford the title compound (1.42 g; 99%). [(M-isobutene)H]+=230/232, [MNa]+=308/310.
93% With triethylamine; In dichloromethane; at 10℃; for 4h; A solution of (3-bromophenyl)methanamine (1 g, 5.37 mmol) in dichloromethane (10 mL) at 10 C. was treated with triethylamine (1 .498 mL, 10.75 mmol) then fe/ -butyl dicarbonate (1 .498 mL, 6.45 mmol) and stirred at 10 C for 4 h. Water (10 mL) was added then the mixture extracted with DCM (2 x 10 mL), washed with brine, dried and evaporated and the residue purified by chromatography (silica gel, 10:1 hexanes/ethyl acetate) to afford the desired product (1 .5 g; 93%) as a colorless solid. NMR (500 MHz, CDCI3) delta ppm 7.43 (s, 1 H), 7.39 (d, J = 6.8 Hz, 1 H), 7.20 (d, J = 6.8 Hz, 2H), 4.89 (s, 1 H), 4.29 (d, J = 5.7 Hz, 2H), 1 .46 (s, 9H).
92% With triethylamine; In dichloromethane; at 20℃; for 5.3h;Cooling with ice; Example 104 Production of tert-Butly N-[(3-bromophenyl)methyl]carbamate. A methylene chloride (40 mL) solution of Boc2O(21.2 g, 97 mmol) was added dropwise to a methylene chloride (160 mL) solution of 3-bromobenzylamine (15.0 g, 81 mmol) and triethylamine (23 mL, 162 mmol) over 20 minutes, under ice-cooling, and the mixture was stirred at room temperature for 5 hours. The reaction mixture was washed with water, and an organic layer was then dried over anhydrous sodium sulfate. n-Hexane was added to the residue obtained by distilling off the solvent under a reduced pressure, and the precipitated solid was collected by filtration, to give the captioned compound (19.8 g, 92%). Mp 41-42C. 1H-NMR (DMSO-d6) delta: 1.39 (s, 9H), 4.12 (d, J=6.1 Hz, 2H), 7.23-7.28 (m, 2H), 7.40-7.42 (m, 3H).
80% With triethylamine; In dichloromethane; at 20℃; To a stirred solution of benzylamine derivative (1 equiv.) in dry DCM, triethylamine (1 .5 equiv.) and di-tert-butyl dicarbonate (1 -1 .2 equiv.) were added under azote atmosphere. The reaction mixture was stirred at room temperature until completion. Water was then added, the phases were separated and the aqueous phase was extracted once with DCM. The combined organic layers were washed with brine, dried over Na2S04, filtered and concentrated under vacuum. The crude mixture was then purified by flash column chromatography (0-10% MeOH in DCM) to provide the expected compound. The following compounds are examples illustrating this procedure:; tert-butyl bomophenyl)methyllcarbamate was prepared from 3- bromobenzylamine (2 g, 10.75 mmol). Yield: 2.47g (80%) of the title compound as a white powder
With sodium hydroxide; In tetrahydrofuran; at 20℃; for 0.5h; A mixture of 3-aminomethylbromobenzene (22.11 g, 99.5 mmol), di-tert-butyl dicarbonate (26.07 g, 119.45 mmol), sodium hydroxide (8.76 g, 219 mmol) in tetrahydrofuran (75 mL) and water (100 mL) were stirred at room temperature for 30 minutes. Extraction and work-up with methylene chloride and water, followed by drying gave tert-butyl (3-bromo-benzyl) carbamate (34.9 g)
Example 95 1-(3-Bromophenyl)-N-methylmethanamine To bromobenzylamine (0.890 g, 4 mmol) in THF (9 mL) was added NaOH (4.20 mL, 1 N, 4.20 mmol) and the solution was stirred at room temperature for 5 mins, when BOC2O (0.975 mL, 4.20 mmol) was added. This mixture was stirred for an additional 30 mins. The reaction mixture was diluted with EtOAc (20 mL). The organic layer was separated, washed with brine (5 mL), dried over Na2SO4, filtered and concentrated. Lithium aluminum hydride (12.00 mL, 12.00 mmol) was added to the above crude product and heated in a microwave at about 100 C. for about 1 h. The reaction mixture was diluted with Et2O (~50 mL) and quenched slowly with Na2SO4 (sat.). The organic layer was separated, dried over, filtered, and concentrated to afford the title compound (0.472 g, 59%). LC-MS m/z 200 (M+H)+.
Example 167 1-(3-Bromophenyl)-N-methylmethanamine To bromobenzylamine (0.890 g, 4 mmol) in THF (9 mL) was added NaOH (4.20 mL, 1 N, 4.20 mmol) and the mixture was stirred at room temperature for 5 min where upon Boc2O (0.975 mL, 4.20 mmol) was added and that mixture was stirred for an additional 30 min. The reaction mixture was diluted with EtOAc (20 mL). The organic layer was separated, washed with brine (5 mL), dried over Na2SO4, filtered and concentrated. LAH (12.00 mL, 12.00 mmol) was added to the above crude product and heated in a microwave at 100 C. for 1 h. The reaction was quenched and diluted with Et2O (~50 mL) and quenched slowly with Na2SO4 (sat.). The organic layer was separated, dried over Na2SO4, filtered, and concentrated to afford the title compound (0.472 g, 59%). LC-MS m/z 200 (M+H)+.
Example 95 l-(3-Bromophenyl)-lambda'-methylmethanamine To bromobenzylamine (0.890 g, 4 mmol) in THF (9 mL) was added NaOH (4.20 mL, 1 N, 4.20 mmol) and the solution was stirred at room temperature for 5 mins, when BOC2O (0.975 mL, 4.20 mmol) was added. This mixture was stirred for an additional 30 mins. The reaction mixture was diluted with EtOAc (20 mL). The organic layer was separated, washed with brine (5 mL), dried over Na2SOzI, filtered and concentrated. Lithium aluminum hydride (12.00 mL, 12.00 mmol) was added to the above crude product and heated in a microwave at about 100 0C for about 1 h. The reaction mixture was diluted with Et2O (-50 mL) and quenched slowly with Na2Stheta4 (sat.). The organic layer was separated, dried over, filtered, and concentrated to afford the title compound (0.472 g, 59%). LC-MS m/z 200 (M+H)+.
With triethylamine; In dichloromethane; at 0 - 20℃; General procedure: (c) A solution of Boc2O (1.29g, 5.91mmol) in CH2Cl2 (10ml) was added to a suspension of 4-bromobenzylamine (1.00g, 5.38mmol) and Et3N (0.60g, 5.91mmol) in CH2Cl2 (10ml) for 5min at 0C with a CaCl2 tube. The reaction mixture was stirred overnight at room temperature. Then, H2O (50ml) was added to the mixture, and the organic layer was separated. The aqueous layer was extracted with CHCl3 (50ml×3). The combined organic layer was washed with H2O (50ml×1) and then brine (50ml×1), dried over Na2SO4 (anhyd), filtered, and concentrated under reduced pressure to afford (4-bromobenzyl)carbamic acid tert-butyl ester (1.63g, quant. y.) as a colorless solid.
With sodium hydrogencarbonate; In tetrahydrofuran; at 20℃; Add m-bromobenzylamine (1.86 g, 10 mmol) to the round bottom flask, dissolve in 100 mL of THF, add sodium bicarbonate (1.68 g, 20 mmol), and add di-tert-butyl dicarbonate (2.4 g, 11 mmol) with stirring,Stir overnight at room temperature, spin off the solution, dissolve the EA, wash with saturated brine three times, dry the organic phase over anhydrous sodium sulfate, spin dry to obtain a white solid, and directly send to the next step

  • 14
  • [ 10269-01-9 ]
  • [ 171663-13-1 ]
YieldReaction ConditionsOperation in experiment
With tert-butyldicarbonate; N-ethyl-N,N-diisopropylamine; In dichloromethane; at 0 - 20℃; 26.25g of 3-Bromobenzylamine hydrochloride was suspended in 250 ml of dichloromethane, and the mixture was cooled to 0C. 33.5 g of N,N-diisopropylethylamine and 28.3 g of t-butyl dicarbonate were added. After stirring was continued at room temperature overnight, the reaction mixture was diluted with ethyl acetate. The solution was washed with water and saturated brine, dried over anhydrous magnesium sulfate, filtered, and the solvent was distilled off, to give 31.28 g of the title compound.1H-NMR (CDCl3) delta : 1.45 (s, 9H) 4.28 (d, J=6.0Hz, 2H) 4.87 (brs, 1H) 7. 20 (m, 2H) 7.38 (m, 1H) 7.43 (brs, 1H)
  • 15
  • [ 75-89-8 ]
  • [ 171663-13-1 ]
  • [ 903556-08-1 ]
YieldReaction ConditionsOperation in experiment
54% With copper(l) iodide; sodium hydride; In tetrahydrofuran; for 17h;Heating / reflux; To a suspension of sodium hydride (95%, 303 mg) in dry tetrahydrofurane (10 mL) was carefully added 2,2,2-trifluoroethanol (719 EL). Then copper(I) iodide (2.29 g) and a solution of the title compound from Step A above (572 mg) in dry tetrahydrofurane (2 mL) were added and the resulting suspension was heated to reflux for 17 h. The mixture was cooled to room temperature, diluted with water (20 mL) and methanol (20 mL) and extracted with ethyl acetate (3×50 mL). The combined organic layers were dried (MgSO4), filtered, concentrated and purified by flash chromatography (silica, cyclohexane/ethyl acetate) to afford the title compound (330 mg; 54%). [(M-isobutene)H]+=250, [MNa]+=328.
  • 16
  • [ 150879-48-4 ]
  • [ 141-78-6 ]
  • [ 171663-13-1 ]
  • [ 214956-91-9 ]
YieldReaction ConditionsOperation in experiment
With n-butyllithium; In tetrahydrofuran; hexane; water; (1) A solution of N-methyl-N-methyloxy-2-amino-5-chlorobenzamide (24.8 g) and <strong>[171663-13-1]N-tert-butoxycarbonyl-3-bromobenzylamine</strong> (22.0 g) in tetrahydrofuran (300 ml) was cooled to -78 C. To the solution was gradually added dropwise a hexane solution (1.6 mol./L)(240 ml) of n-butyl lithium. To the mixture were then added water (300 ml) and acetic acid ethyl ester (300 ml). The organic layer was washed with water, which was dried over anhydrous MgSO4, then the solvent was distilled off. To the residual oily compound was added hexane (400 ml) to cause crystallization. The crystalline product was collected by filtration to give 2-amino-3'-tert-butoxycarbonylaminomethyl-5-chlorobenzophenone (12.5 g) as pale yellow crystals.
  • 17
  • [ 214971-18-3 ]
  • [ 171663-13-1 ]
  • 2-amino-3-tert-butoxycarbonylaminomethyl-4-chlorobenzophenone [ No CAS ]
YieldReaction ConditionsOperation in experiment
With n-butyllithium; In tetrahydrofuran; water; (2) N-methyl-N-methyloxy-2-amino-4-chlorobenzamide (3.6 g) and <strong>[171663-13-1]N-tert-butoxycarbonyl-3-bromobenzylamine</strong> (5.5 g) were dissolved in tetrahydrofuran (50 ml). The solution was cooled to -78 C., to which was added dropwise, while stirring, a hexane solution of n-butyl lithium (1.6 mol/L, 60 ml) over 40 minutes. To the reaction mixture was added water, which was subjected to extraction with ethyl acetate (150 ml). The organic layer was washed with water and dried over anhydrous sodium sulfate. The solvent was distilled off. The residue was purified by means of a silica gel column chromatography to give 2-amino-3-tert-butoxycarbonylaminomethyl-4-chlorobenzophenone as a yellow oily product (2.3 g). NMR(CDCL3) delta: 1.456(9H,s), 4.37(2H,d,J=5.8 Hz), 4.92(1H, m), 6.197(2H,br), 6.50-6.80(2H,m), 7.30-7.60(5H,m)
  • 18
  • [ 214957-91-2 ]
  • [ 171663-13-1 ]
  • [ 214957-92-3 ]
YieldReaction ConditionsOperation in experiment
With n-butyllithium; In tetrahydrofuran; hexane; water; ethyl acetate; (4) N-Methyl-N-methyloxy-2-amino-5-(3-phenylpropyloxy)benzamide (1.0 g) and N-tert-butoxycarbonyl 3-bromobenzylamine (0.92 g) were dissolved in tetrahydrofuran (20 ml). The solution was cooled to -70 C., to which was added dropwise, while stirring, 12 ml of a hexane solution of n-butyl lithium (1.6 mol/L) over 20 minutes. To the mixture was then added water (50 ml) and ethyl acetate (50 ml). The organic layer was washed with water and dried over anhydrous sodium sulfate. The solvent was distilled off, and the residue was purified by means of a silica gel column chromatography to give 2-amino-3'-tert-butoxycarbonylaminomethyl-5-(3-phenylpropyloxy)benzophenone as a yellow oily product (0.75 g). NMR(CDCl3) delta: 1.451(9H,s), 1.9-2.1(2H,m), 2.751(2H,t, J=8.2 Hz), 3.779(2H,t,J=6.2 Hz), 4.37(2H,d,J=6.2 Hz), 4.87 (1H,m), 5.719(2H,m), 6.7-7.6(12H,m)
  • 19
  • [ 1436415-17-6 ]
  • [ 171663-13-1 ]
  • [ 214960-22-2 ]
YieldReaction ConditionsOperation in experiment
With n-butyllithium; In tetrahydrofuran; water; ethyl acetate; (3) N-Methyl-N-methyloxy-2-amino-5-isobutyloxybenzamide (0.6 g) and N-tert-butoxycarbonyl 3-bromobenzylamine (0.76 g) were dissolved in tetrahydrofuran (18 ml). The solution was cooled to -78 C., to which was added dropwise, while stirring, 9 ml of a hexanoic solution of n-butyl lithium (1.6 mol./L) over 20 minutes. To the reaction mixture were added water (50 ml) and ethyl acetate (50 ml). The organic layer was washed with water and dried over anhydrous sodium sulfate. The solvent was distilled off. The residue was purified by means of a silica gel column chromatography to give 2-amino-3'-tert-butoxycarbonylaminomethyl-5-isobutyloxy-benzophenone as a yellow oily product (0.38 g). NMR(CDCl3) delta: 0.95(6H,d,J=6.6 Hz), 1.455(9H,s), 2.0(1H,m), 3.56(2H,d,J=6.6 Hz), 4.41(2H,d,J=6.2 Hz), 4.90(1H,m), 5.70(2H,m), 6.65-7.6(7H,m)
  • 20
  • [ 214971-09-2 ]
  • [ 171663-13-1 ]
  • 2-amino-3-tert-butoxycarbonylaminomethyl-5-methyloxy-benzophenone [ No CAS ]
YieldReaction ConditionsOperation in experiment
With n-butyllithium; In tetrahydrofuran; water; ethyl acetate; (3) A tetrahydrofuran (15 ml) solution of N-methyl-N-methyloxy-2-amino-5-methyloxy-benzamide (0.35 g) and <strong>[171663-13-1]N-tert-butoxycarbonyl-3-bromobenzylamine</strong> (0.48 g) was cooled to -70 C. To the solution was added dropwise, while stirring, a hexane solution of n-butyl lithium (1.6 mol/L) (6.2 ml) over 20 minutes. To the mixture were then added water (40 ml) and ethyl acetate (40 ml). The organic layer was washed with water and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure. The residue was purified by means of a silica gel column chromatography to give 2-amino-3-tert-butoxycarbonylaminomethyl-5-methyloxy-benzophenone as a yellow oily product (0.18 g). NMR(CDCl3) delta: 1.453(9H,s), 3.66(3H,s), 4.38(2H,d, J=6.2 Hz), 4.92(1H,m), 5.33(2H,m), 6.7-7.65(7H,m)
  • 21
  • [ 171663-13-1 ]
  • [ 1066-54-2 ]
  • [ 913073-73-1 ]
YieldReaction ConditionsOperation in experiment
67% With triethylamine;bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; at 90℃; for 18.08h; Example 2.36: tert-butyl 4-(3-ethynylbenzyIammo)-3-hydroxy-l-phenylbutan-2- ylcarbamate:; [0280] To <strong>[171663-13-1]tert-butyl 3-bromobenzylcarbamate</strong> (220 mg, 1 mmol) in triethylamine (3 ml), trimethylsilyl acetylene (147mg, 1.5 mmol) was added followed by cuprous iodide (8mg, 0.04 mmol). After stirring for 5 min, dichloro bis (triphenylphosphine) palladium (II) (35 mg, 0.05 mmol) was added and the reaction mixture was heated at 9O0C for 18h. Then the reaction mixture was filtered, diluted with ethyl acetate and washed with water. Organic layer was dried, evaporated and the crude residue was purified by column chromatography to obtain tert-butyl 3-((trimethylsilyl)ethynyl)benzylcarbamate in 67% yield.
  • 22
  • [ 71597-85-8 ]
  • [ 171663-13-1 ]
  • [ 808769-21-3 ]
YieldReaction ConditionsOperation in experiment
Preparation 12 : tert-Butyl [(4'-hydroxybiphenyl-3-yl)methyl]carbamate; Nitrogen was bubbled through a stirred solution of the bromide from preparation 11 (5.12Kg; 17.9 mol), 4-hydroxyphenylboronic acid (2.71 Kg; 19.7 mol) and sodium carbonate (2.848Kg; 26.8 mol) in a mixture of 1 ,4 dioxane (25.6L) and demineralised water (25.6L) at 20 to 250C for 1 hour. Then 1,1'-/s(diphenylphosphino)ferrocenyl palladium(ll)chloride(14.6g; 0.0179 mol) was added to the mixture and the nitrogen bubbling was continued for a further 30 minutes. Subsequently, the reaction was heated at 65 to 7O0C under a nitrogen blanket for 2 hours. The reaction was cooled to 20 to 25C, ethyl acetate (41 L) was added and the resulting mixture was stirred vigorously for 10 minutes, the phases were then separated. The organic phase was washed with a solution of citric acid (1.9Kg) in demineralised water (18.9L) followed by a solution of sodium chloride (3.15Kg) in demineralised water (18.9L). The ethyl acetate solution was treated with activated carbon (Darco KB 100mesh, wet powder; 5.12Kg) and stirred for 12 hours. The EPO <DP n="35"/>resulting slurry was then filtered through Arbocel and the cake was washed with methanol (25.6L). The combined filtrate was distilled and replaced with toluene under reduced pressure at 40 to 500C to a final volume of approximately 15L. The solution was then cooled to 10C over 2 hours and the resulting suspension was stirred at 1O0C for 12 hours. The product was isolated by filtration and washed with cyclohexane (2 x 2.56L) to provide the title compound as a white solid (4.26 Kg).1H NMR (400MHz1 CDCI3) delta: 1.47 (s, 9H), 4.33-4.41 (m, 2H), 4.87-4.94 (bs, 1H), 6.89 (d, 2H), 7.21 (d, 1H), 7.37 (dd, 1H), 7.43-7.45 (m, 4H) ppm. MS (electrospray) m/z 298 [M-H]", 322 [M+Na]+
  • 23
  • [ 39959-54-1 ]
  • [ 171663-13-1 ]
YieldReaction ConditionsOperation in experiment
(a) tert-Butyl (3-bromo benzyl)carbamate In a manner similar to that of Example 1(a), starting with 50 g (220 mmol) of 3-bromobenzylamine hydrochloride, 65.1 g (100%) of the expected product are obtained in the form of a pale brown solid.
  • 24
  • [ 107-08-4 ]
  • [ 171663-13-1 ]
  • [ 398150-56-6 ]
YieldReaction ConditionsOperation in experiment
(a) tert-Butyl (3-bromo benzyl)propylcarbamate In a manner similar to that of Example 17(d), starting with 3 g (10.5 mmol) of tert-butyl (3-bromo-benzyl) carbamate and 1.15 ml (11.5 mmol) of iodopropane, 3.35 g (97%) of the desired product are obtained.
  • 25
  • [ 171663-13-1 ]
  • [ 317358-61-5 ]
YieldReaction ConditionsOperation in experiment
(b) tert-Butyl (3-bromo benzyl)-N-methylcarbamate In a manner similar to that of Example 1(b), starting with 85 g (297 mmol) of tert-butyl (3-bromo benzyl)carbamate, 92.5 g (100%) of the expected product are obtained.
  • 26
  • [ 2295-31-0 ]
  • [ 328125-41-3 ]
  • [ 171663-13-1 ]
  • tert-butyl [4'-(2,4-dioxothiazolidin-5-ylidenemethyl)biphenyl-3-ylmethyl]carbamate [ No CAS ]
YieldReaction ConditionsOperation in experiment
(a) tert-Butyl [4'-(2,4-dioxothiazolidin-5-ylidenemethyl)biphenyl-3-ylmethyl]carbamate In a manner similar to that of Example 1(f) by reacting 7.4 g (24 mmol) of tert-butyl (4'-formyl-biphenyl-3-ylmethyl)carbamate (prepared as in Example 1(e) from tert-butyl (3-bromo benzyl)carbamate)with 2.8 g (24 mmol) of 2,4-thiazolidine dione, 9 g (95%) of the expected product are obtained.
  • 27
  • [ 4394-85-8 ]
  • [ 171663-13-1 ]
  • [ 170853-04-0 ]
YieldReaction ConditionsOperation in experiment
8.58g of t-Butyl N-(3-bromobenzyl)carbamate was dissolved in 100 ml of tetrahydrofuran, and the mixture was cooled to -78C under nitrogen atmosphere. 41 ml of butyl lithium (1.56 M solution in hexane) was added. After stirring was continued for 30 minutes, 6.91 g of N-formylmorpholine was added. After stirring was continued at -78C for 30 minutes, 1N-hydrochloric acid was added, and the mixture was extracted with ethyl acetate. The solution was dried over anhydrous magnesium sulfate, filtered, and the solvent was distilled off, and the residue was purified by silica gel column chromatography, to give 4.762 g of the title compound in the 3:1 ? 3:2 hexane-ethyl acetate fraction.1H-NMR (CDCl3) delta : 1.44 (s, 9H) 4.40 (d, J=6.0Hz, 2H) 4.95 (br, 1H) 7.50 (m, 1H) 7.56-7.59 (m, 1H) 7.78-7.80 (m, 1H) 7.80 (s, 1H) 10.01 (s, 1H)
  • 28
  • [ 171663-13-1 ]
  • [ 411235-57-9 ]
  • [ 1108723-65-4 ]
YieldReaction ConditionsOperation in experiment
93% With potassium phosphate;palladium diacetate; tricyclohexylphosphine; In water; toluene; at 100℃; for 3h; Example 1.1.22: (3-cyclopropylphenyl)methanamine; To a solution of <strong>[171663-13-1]tert-butyl 3-bromobenzylcarbamate</strong> (572 mg, 2 mmol), cyclopropyl boronic acid (223 mg, 2.6 mmol), potassium phosphate (1.49 g, 7.0 mmol) and tricyclohexyl phosphine (56 mg, 0.2 mmol)in toluene (9 mL) and water (0.45 mL) under a nitrogen atmosphere was added palladium acetate (22mg, 0.1 mmol). The mixture was heated at 1000C for 3h and then cooled to rt. Water (20 mL) was added and the mixture extracted with EtOAc (2x30 mL), the combined organic extracts were washed with brine (20 mL), dried over Na2SO4 and concentrated in vacuo. Crude product was purified by column chromatography (15% EtOAc in hexanes) afforded tert-butyl 3-cyclopropylbenzylcarbamate as a colorless oil in 93% yield. (3-cyclopropylphenyl)methanamine was then generated by removing the Boc protecting group by treatment with HCl (in methanol or dioxane) or trifluoroacetic acid in dichloromethane.
 

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