[ CAS No. 635319-09-4 ] {[proInfo.proName]}

Name: 635319-09-4|(3R,4R)-tert-Butyl 3-hydroxy-4-(hydroxymethyl)pyrrolidine-1-carboxylate|97%
Brand: Ambeed
SKU: A779920
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Quality Control of [ 635319-09-4 ]

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Product Details of [ 635319-09-4 ]

CAS No. :	635319-09-4	MDL No. :	MFCD18071964
Formula :	C₁₀H₁₉NO₄	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	BSTWKRUNXOFBPE-SFYZADRCSA-N
M.W :	217.26	Pubchem ID :	11252928
Synonyms :

Safety of [ 635319-09-4 ]

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

Application In Synthesis of [ 635319-09-4 ]

* 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 [ 635319-09-4 ]
Downstream synthetic route of [ 635319-09-4 ]

[ 635319-09-4 ] Synthesis Path-Upstream 1~8

1
[ 635319-08-3 ]
[ 635319-09-4 ]

Yield	Reaction Conditions	Operation in experiment
92%	Stage #1: With sodium periodate In ethanol; water at 0℃; for 0.333333 h; Stage #2: With sodium tetrahydroborate In ethanol; water at 0℃;	). <P>N-TERT-BUTOXYCARBONYL- (3R, 4S)-3-HYDROXY-4- [ ( S)-1, 2-DIHYDROXYETHYL] PYRROLIDINE] (3.4 g, 13.7 [MMOL)] in ethanol (50 mL) was added dropwise to a stirred solution of sodium periodate (3.4 g, 16 [MMOL)] in water (25 mL) while maintaining the reaction temperature at 0 [°C.] The reaction was left an additional 20 min after which time sodium borohydride (2.0 g, excess) was added portionwise while again ensuring the reaction temperature was maintained at 0 [°C.] On complete addition the solid was filtered, washed with ethanol (50 mL) and concentrated in vacuo to afford a syrup. Chromatography afforded 1 (2.74 g, 92percent) as a syrup.

Reference： [1] Journal of Medicinal Chemistry, 2003, vol. 46, # 24, p. 5271 - 5276
[2] Patent: WO2004/18496, 2004, A1, . Location in patent: Page 23-24

2
[ 253129-03-2 ]
[ 24424-99-5 ]
[ 635319-09-4 ]

Yield	Reaction Conditions	Operation in experiment
100%	With hydrogen In methanol for 24 h;	10percent Pd-C (300 mg) was added to a stirred solution of (3R, 4R)-1-N-BENZYL-3- hydroxy-4-hydroxymethylpyrrolidine from example 6 (4,1. 49 g, 7.19 MMOL) and di-tert-butyl dicarbonate (1.63 g, 7.47 MMOL) in MEOH (30 mL) and hydrogen added from a balloon for 24 h. The mixture was filtered through Celite, evaporated and the residue chromatographed (eluant ethyl acetate- methanol19 : 1, v/v) to afford (3R, 4R)-3-HYDROXY-4-HYDROXYMETHYLPYRROLIDIN-1- N-carboxylic acid tert-butyl ester (14) as a colourless gum (1.56 g, 100percent). [a] 21 +16° (c 1.09, MEOH). A sample prepared as in G. B. Evans, R. H. Furneaux, A. Lewandocwicz, V. L. Schramm and P. C. Tyler, J. Med. CHEM., 2003,46, 5271, ultimately derived from D-xylose, had [A] 21 +16° (c 0.795, MEOH).
100%	With hydrogen In methanol for 24 h;	tert-Butyl(3R,4R)-3-hydroxy-4-(hydroxymethyl)pyrrolidine-1-carboxylate[(+)-7]A. From diol (+)-3. Pd-C (300 mg, 10percent) was added to a stirred solution of the diol (+)-3 (1.49 g, 7.19 mmol) and di-ferf-butyl dicarbonate (1.63 g, 7.47 mmol) in MeOH (30 ml), and hydrogen was added from a balloon over 24 h. The mixture was filtered through Celite^.(R)., the solvent was evaporated and the residue was chromatographed (EtOAc-MeOH, 19 : 1) to afford the /V-Boc protected pyrrolidine (+)-7 as a colourless gum (1.56 g, 100percent), [α]_p + 15.9(c 1.09, MeOH), in good agreement with the value derived from the sample made by method B.

Reference： [1] Organic and Biomolecular Chemistry, 2006, vol. 4, # 6, p. 1131 - 1139
[2] Patent: WO2005/33076, 2005, A1, . Location in patent: Page/Page column 30
[3] Patent: WO2007/69923, 2007, A1, . Location in patent: Page/Page column 18; 21
[4] Organic and Biomolecular Chemistry, 2007, vol. 5, # 17, p. 2800 - 2802

3
[ 24424-99-5 ]
[ 267421-93-2 ]
[ 635319-09-4 ]

Reference： [1] Patent: WO2005/118532, 2005, A1, . Location in patent: Page/Page column 23
[2] Patent: WO2014/73989, 2014, A1, . Location in patent: Page/Page column 25; 35; 36
[3] Patent: WO2016/187183, 2016, A1, . Location in patent: Paragraph 0062

4
[ 849935-77-9 ]
[ 635319-09-4 ]

Reference： [1] Organic and Biomolecular Chemistry, 2006, vol. 4, # 6, p. 1131 - 1139

5
[ 24424-99-5 ]
[ 635319-09-4 ]

Reference： [1] Organic and Biomolecular Chemistry, 2006, vol. 4, # 6, p. 1131 - 1139
[2] Journal of Medicinal Chemistry, 2003, vol. 46, # 24, p. 5271 - 5276

6
[ 253129-03-2 ]
[ 635319-09-4 ]

Reference： [1] Patent: WO2014/73989, 2014, A1,
[2] Patent: WO2016/187183, 2016, A1,

7
[ 71336-69-1 ]
[ 635319-09-4 ]

Reference： [1] Patent: WO2016/187183, 2016, A1,

8
[ 871086-00-9 ]
[ 635319-09-4 ]

Reference： [1] Patent: WO2016/187183, 2016, A1,

[ 635319-09-4 ] Synthesis Path-Downstream 1~87

1
[ 124-63-0 ]
[ 635319-09-4 ]
[ 666831-24-9 ]

Yield	Reaction Conditions	Operation in experiment
68%	With N-ethyl-N,N-diisopropylamine; In dichloromethane; at -78℃; for 0.75h;	Methanesulfonyl chloride (0.950 mL, 12.3 MMOL) was added to a solution of (3R, 4R)-N-TERT-BUTOXYCARBONYL-3-HYDROXY-4-HYDROXYMETHYL-PYRROLIDINE (29) (Evans et AL., J. Med. CHEM., 2003, 46, 5271-5276) (2.16 g, 9.94 MMOL) and DIISOPROPYLETHYL amine (2.65 mL, 15.0 MMOL) in DCM (40 mL) cooled to-78 C over 5 min. After stirring at-78 C for 40 min, aqueous 2M HCI was added, the organic phase was separated. The aqueous phase was extracted with DCM (x2). The combined organic extract was washed with sat. aqueous NAHC03 then brine and dried (MGS04). Normal processing and chromatography gave (1.99 g, 6.74 mmol, 68%) of MESYLATE 30 as a colourless glass. HRMS (MH+) calc for C11H21NO6SNA : 318.0982. Found 318.0979. A solution of MESYLATE 30 (450 mg, 1.53 MMOL) in DMF (5 mL) was added to a stirred solution of sodium thiomethoxide (200 mg, 2.85 MMOL) in DMF (3 mL) and the mixture was stirred for 1 h. Toluene (50 mL) and H2O (50 mL) were added and shaken, the phases separated, the organic layer dried (MGS04) and the solvent removed at reduced pressure. The crude product that was purified by chromatography on silica, eluting with 10-50% EtOAc/petroleum ether to afford intermediate 31 (210 mg, 0.849 MMOL, 55%). A solution of this material in methanol (3 mL) was treated with CHCI (1 mL). After 1 h, the solution was concentrated to dryness to give title compound 32 as a solid residue (0.830 mmol, 98%). The solid residue was dissolved in H2O (10 ML) or D20 (for NMR samples) and the solvent removed (X3). H NMR (D2O) 4.40 (q, J = 3.1 Hz, 1H), 3.67 (dd, J = 12.0, 6.6 Hz, 1H), 3.50 (dd, J= 12.8, 5.1 Hz, 1H), 3.28 (dd, J= 12.8, 3.0 Hz, 1H), 3.22 (dd, J= 8.7, 3.4 Hz, 1H), 2.73-2. 66 (m, 1H), 2.58-2. 50 (m, 2H), 2.40-2. 30 (m, 2H) 2.13 (s, 3H). 13C NMR (D20) 73.5, 51.5, 48.6, 45.2, 34.3, 14.9.
60%	With N-ethyl-N,N-diisopropylamine; In dichloromethane; at -60℃; for 0.583333h;Inert atmosphere;	[0073] tert-Butyl (3R,4S)-3-hydroxy-4-[(pyridin-2-ylthio)methyl]pyrrolidine-l- carboxylate (23). Step 1. tert-Butyl (3R,4R)-3-hydroxy-4-(hydroxymethyl)pyrrolidine-l- carboxylate (1) [Clinch, et al.37] (10.00 g, 46.03 mmol) and N,N'-diisopropylethylamine (16.2 mL, 92.06 mmol) were dissolved in CH2CI2 (300 mL) and cooled to -60 C. Methanesulfonyl chloride (3.45 mL, 44.61 mmol) was added dropwise. After 30 min more methanesulfonyl chloride (0.60 mL) added and the mixture stirred a further 5 min then warmed to 0 C and washed with sat. aq NaHCC^ (3 x 30 mL), dried and the solvent evaporated. The residue was chromatographed on silica gel (gradient of 50 - 100% EtOAc in hexanes then 0 - 1% MeOH in EtOAc) to give the mesylate 2 as a yellow oil (8.18 g, 60%).
	With triethylamine; In dichloromethane; at 0 - 20℃;	Methanesulfonyl chloride (180 muL, 23 [MMOL)] was added dropwise to a [CH2C12] solution [OF TRIETHYLAMINE (400, UL,] 29 [MMOL)] and (3R, [4R)-1-TERT-BUTOXYCARBONYL-3-] [HYDROXY-4- (HYDROXYMETHYL) PYRROLIDINE] (1) (2 g, 9.2 [MMOL)] at 0 C and the resulting solution allowed to warm to room temperature. The reaction was diluted with CH2CI2, washed with water, brine, dried [(MGS04)] and concentrated in vacuo. The resulting residue was purified by silica gel flash chromatography to afford (3R, [4R)-1-TERT-BUTOXYCARBONYL-3-HYDROXY-4- (MESYLOXYMETHYL) PYRROLIDINE] (900 mg) as an oil. Without further purification the product was dissolved in DMF (10 mL) and stirred with sodium thiomethoxide (400 mg, 5.7 [MMOL)] at room temp. overnight. The reaction was diluted with toluene washed with water, brine, dried [(MGS04)] and concentrated in vacuo. The resulting residue was purified by silica gel flash chromatography to afford (3R, [4S)-1-TERT-BUTOXYCARBONYL-3-HYDROXY-4-] (methylthiomethyl) pyrrolidine (600 mg, 2.4 [MMOL)] as a syrup, which was not further characterised. (3R, [4S)-1-TERT-BUTOXYCARBONYL-3-HYDROXY-4-] (methylthio) pyrrolidine was dissolved in [MEOH] (5.0 mL) and [CHCI] (1.0 mL) and concentrated in vacuo to afford (3R, 4S)-3-hydroxy-4- (methylthiomethyl) pyrrolidine hydrochloride (48) as a syrup (442 mg, 26% overall yield for three [STEPS).'3C] NMR [(D20)] 8 73.5, 51.5, 48.6, 45.2, 34.3, 14.9.

Reference： [1]Patent: WO2004/69856,2004,A1 .Location in patent: Page 22
[2]Patent: WO2014/25842,2014,A1 .Location in patent: Paragraph 0072; 0073
[3]Journal of the American Chemical Society,2015,vol. 137,p. 14275 - 14280
[4]Journal of Medicinal Chemistry,2005,vol. 48,p. 4679 - 4689
[5]Patent: WO2004/18496,2004,A1 .Location in patent: Page 45
[6]Patent: WO2016/187183,2016,A1 .Location in patent: Paragraph 0062

2
[ 58479-61-1 ]
[ 635319-09-4 ]
[ 858930-18-4 ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 4679 - 4689

3
[ 253129-03-2 ]
[ 24424-99-5 ]
[ 635319-09-4 ]

Yield	Reaction Conditions	Operation in experiment
100%	With hydrogen;palladium 10% on activated carbon; In methanol; for 24h;	10% Pd-C (300 mg) was added to a stirred solution of (3R, 4R)-1-N-BENZYL-3- hydroxy-4-hydroxymethylpyrrolidine from example 6 (4,1. 49 g, 7.19 MMOL) and di-tert-butyl dicarbonate (1.63 g, 7.47 MMOL) in MEOH (30 mL) and hydrogen added from a balloon for 24 h. The mixture was filtered through Celite, evaporated and the residue chromatographed (eluant ethyl acetate- methanol19 : 1, v/v) to afford (3R, 4R)-3-HYDROXY-4-HYDROXYMETHYLPYRROLIDIN-1- N-carboxylic acid tert-butyl ester (14) as a colourless gum (1.56 g, 100%). [a] 21 +16 (c 1.09, MEOH). A sample prepared as in G. B. Evans, R. H. Furneaux, A. Lewandocwicz, V. L. Schramm and P. C. Tyler, J. Med. CHEM., 2003,46, 5271, ultimately derived from D-xylose, had [A] 21 +16 (c 0.795, MEOH).
100%	With hydrogen;palladium 10% on activated carbon; In methanol; for 24h;Product distribution / selectivity;	tert-Butyl(3R,4R)-3-hydroxy-4-(hydroxymethyl)pyrrolidine-1-carboxylate[(+)-7]A. From diol (+)-3. Pd-C (300 mg, 10%) was added to a stirred solution of the diol (+)-3 (1.49 g, 7.19 mmol) and di-ferf-butyl dicarbonate (1.63 g, 7.47 mmol) in MeOH (30 ml), and hydrogen was added from a balloon over 24 h. The mixture was filtered through Celite, the solvent was evaporated and the residue was chromatographed (EtOAc-MeOH, 19 : 1) to afford the /V-Boc protected pyrrolidine (+)-7 as a colourless gum (1.56 g, 100%), [alpha]p + 15.9(c 1.09, MeOH), in good agreement with the value derived from the sample made by method B.

Reference： [1]Organic and Biomolecular Chemistry,2006,vol. 4,p. 1131 - 1139
[2]Patent: WO2005/33076,2005,A1 .Location in patent: Page/Page column 30
[3]Patent: WO2007/69923,2007,A1 .Location in patent: Page/Page column 18; 21
[4]Organic and Biomolecular Chemistry,2007,vol. 5,p. 2800 - 2802

4
C₁₂H₂₃NO₆ [ No CAS ]
[ 635319-09-4 ]

Reference： [1]Organic and Biomolecular Chemistry,2006,vol. 4,p. 1131 - 1139

5
[ 24424-99-5 ]
[ 267421-93-2 ]
[ 635319-09-4 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; In methanol; at 20℃; for 1h;	Example 5; (3R,4R)-1-N-tert-Butoxycarbonyl-3-hydroxy-4-hydroxymethyl-pyrrolidine [(+)-8].; Crude (+) -7 from the previous step (60 g) was taken up in methanol (800 mL), 10% Pd/C (12 g, wet Degussa type) added and the mixture stirred under an atmosphere of hydrogen for 12 h to give crude (3R,4R)-3-Hydroxy-4-hydroxymethyl-pyrrolidine (+)-1. The catalyst was removed by filtration and to the solution in methanol was added triethylamine (30 mL, 216 mmol) and di-tert-butyl dicarbonate (47.5 g, 218 mmol) and the mixture was stirred at room temperature for 1 h (slight exotherm). The mixture was then preabsorbed onto silica and chromatographed by dry-flash chromatography (eluant: CHCl3: EtOAc:MeOH, 5: 2:1 v/v/v) to give (+) -8 as a light orange syrup (25.4 g, 59% from (+) -6). The final product contained about 15 % (w/w) of a triethylammonium salt which could be removed by column chromatography on silica (hexanes: ethyl acetate, 1:4). The data for fully purified (+) -8 is as follows: [alpha]20D +15.4 (c = 0.5, MeOH). 'H NMR (MeOH- d4): No. ppm: 4.14 (m, 1 H), 3.58-3.45 (m, 4H), 3.24-3.18 (m, 2H), 2.24 (m, 1 H), 1.46 (s, 9H). ¹3C NMR (MeOH-d4): 6 ppm (some peaks are doubled due to slow interconversion of rotamers) : 156.99,81.31, (73.10,72.40), 63.06, (54.45,54.03), (50.42,49.75), (48.47, 48.03), 29.18.
1 g	With dmap;	Compound (VIII) (which can be prepared as described in WO 2005/118532) (1 g, 4.82 mmol) in ethanol (10 ml) is degassed and then treated with Pearlman's catalyst (0.1 g). The mixture is stirred under low pressure of hydrogen and the reaction progress is monitored by TLC, more catalyst (0.1 g) is added if the reaction stalls. Once the starting /V-benzyl material is consumed, the mixture is filtered through a pad of filter aid and di-t-butyl dicarbonate (1 .26 g in total, 5.79 mmol) is added to the filtrate, gas evolution and a mild exotherm are observed. Once off- gassing has subsided, DMAP (13 mg) is added resulting in further off-gassing. Once gas evolution has stopped, the solvent is removed in vacuo to give 1g of colourless oil. 6H(500 MHz, CD3OD) 1.45 (9H, s), 2.23 (1 H, m), 3.21 (2H, m), 3.45 (1 H, m), 3.54 (3H, m), 4.13 (1 H, m).

Reference： [1]Patent: WO2005/118532,2005,A1 .Location in patent: Page/Page column 23
[2]Patent: WO2014/73989,2014,A1 .Location in patent: Page/Page column 25; 35; 36
[3]Patent: WO2016/187183,2016,A1 .Location in patent: Paragraph 0062

6
ethyl (RS,SR)-1-benzyl-4-hydroxypyrrolidine-3-carboxylate [ No CAS ]
[ 635319-09-4 ]

Reference： [1]Organic and Biomolecular Chemistry,2006,vol. 4,p. 1131 - 1139

7
[ 849935-77-9 ]
[ 635319-09-4 ]

Reference： [1]Organic and Biomolecular Chemistry,2006,vol. 4,p. 1131 - 1139

8
[ 24424-99-5 ]
[ 635319-09-4 ]

Reference： [1]Organic and Biomolecular Chemistry,2006,vol. 4,p. 1131 - 1139
[2]Journal of Medicinal Chemistry,2003,vol. 46,p. 5271 - 5276

9
[ 635319-09-4 ]
[ 666831-26-1 ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 4679 - 4689

10
[ 635319-09-4 ]
[ 858930-20-8 ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 4679 - 4689

11
[ 635319-09-4 ]
(3S,4R)-3-Ethylsulfanylmethyl-4-hydroxy-pyrrolidine-1-carboxylic acid tert-butyl ester [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 4679 - 4689

12
[ 635319-09-4 ]
[ 742079-57-8 ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 4679 - 4689

13
[ 635319-09-4 ]
[ 742079-58-9 ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 4679 - 4689

14
[ 635319-09-4 ]
(3R,4S)-3-Hydroxy-4-propylsulfanylmethyl-pyrrolidine-1-carboxylic acid tert-butyl ester [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 4679 - 4689

15
[ 635319-09-4 ]
(3S,4R)-3-Butylsulfanylmethyl-4-hydroxy-pyrrolidine-1-carboxylic acid tert-butyl ester [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 4679 - 4689

16
[ 635319-09-4 ]
(3R,4S)-3-Hydroxy-4-phenylsulfanylmethyl-pyrrolidine-1-carboxylic acid tert-butyl ester [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 4679 - 4689

17
[ 635319-09-4 ]
(3R,4S)-3-Hydroxy-4-(pyridin-4-ylsulfanylmethyl)-pyrrolidine-1-carboxylic acid tert-butyl ester [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 4679 - 4689

18
[ 635319-09-4 ]
3R,4S-4-benzylthiomethyl-1-tert-butoxycarbonyl-3-hydroxypyrrolidine [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 4679 - 4689

19
[ 635319-09-4 ]
[ 858930-21-9 ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 4679 - 4689

20
[ 635319-09-4 ]
(3S,4R)-3-(4-Chloro-phenylsulfanylmethyl)-4-hydroxy-pyrrolidine-1-carboxylic acid tert-butyl ester [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 4679 - 4689

21
[ 635319-09-4 ]
(3S,4R)-3-(3-Chloro-phenylsulfanylmethyl)-4-hydroxy-pyrrolidine-1-carboxylic acid tert-butyl ester [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 4679 - 4689

22
[ 635319-09-4 ]
(3S,4R)-3-(4-Fluoro-phenylsulfanylmethyl)-4-hydroxy-pyrrolidine-1-carboxylic acid tert-butyl ester [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 4679 - 4689

23
[ 635319-09-4 ]
[ 742079-59-0 ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 4679 - 4689

24
[ 635319-09-4 ]
(3R,4S)-1-((4-amino-5H-pyrrolo[3,2-d]pyrimidin-7-yl)methyl)-4-((methylthio)methyl)pyrrolidin-3-ol [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 4679 - 4689
[2]Journal of Medicinal Chemistry,2005,vol. 48,p. 4679 - 4689
[3]Patent: WO2014/73989,2014,A1
[4]Patent: WO2016/187183,2016,A1

25
[ 635319-09-4 ]
(3R,4S)-3-hydroxy-4-methylthiomethylpyrrolidine hydrochloride [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 4679 - 4689
[2]Patent: WO2016/187183,2016,A1

26
[ 635319-09-4 ]
(3R,4S)-1-[(9-deazaadenin-9-yl)methyl]-3-hydroxy-4-(ethylthiomethyl)pyrrolidine [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 4679 - 4689

27
[ 635319-09-4 ]
(3R,4S)-1-[(9-deazaadenin-9-yl)methyl]-3-hydroxy-4-(isopropylthiomethyl)pyrrolidine [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 4679 - 4689

28
[ 635319-09-4 ]
(3R,4S)-4-ethythiomethyl-3-hydroxypyrrolidine hydrochloride [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 4679 - 4689

29
[ 635319-09-4 ]
(3R,4S)-3-hydroxy-4-(2-propylthiomethyl)pyrrolidine hydrochloride [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 4679 - 4689

30
[ 635319-09-4 ]
(3R,4S)-1-[(9-deazaadenin-9-yl)methyl]-3-hydroxy-4-(1-propylthiomethyl)pyrrolidine [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 4679 - 4689

31
[ 635319-09-4 ]
(3R,4S)-3-hydroxy-4-(1-propylthiomethyl)pyrrolidine hydrochloride [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 4679 - 4689

32
[ 635319-09-4 ]
(3R,4S)-1-[(9-deazaadenin-9-yl)methyl]-3-hydroxy-4-(phenylthiomethyl)pyrrolidine [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 4679 - 4689

33
[ 635319-09-4 ]
(3R,4S)-4-(1-butylthiomethyl)-1-[(9-deazaadenin-9-yl)methyl]-3-hydroxypyrrolidine [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 4679 - 4689

34
[ 635319-09-4 ]
(3R,4S)-4-butylthiomethyl-3-hydroxypyrrolidine hydrochloride [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 4679 - 4689

35
[ 635319-09-4 ]
(3R,4S)-3-hydroxy-4-phenylthiomethylpyrrolidine hydrochloride [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 4679 - 4689

36
[ 635319-09-4 ]
(3R,4S)-3-hydroxy-4-(4-pyridylthiomethyl)pyrrolidine hydrchloride [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 4679 - 4689

37
[ 635319-09-4 ]
(3R,4S)-1-[(9-deazaadenin-9-yl)methyl]-3-hydroxy-4-(4-pyrridylthiomethyl)pyrrolidine [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 4679 - 4689

38
[ 635319-09-4 ]
(3R,4S)-1-[(9-deazaadenin-9-yl)methyl]-4-(4-fluorophenylthiomethyl)-3-hydroxypyrrolidine [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 4679 - 4689

39
[ 635319-09-4 ]
(3R,4S)-4-(4-fluorophenylthiomethyl)-3-hydroxypyrrolidine hydrochloride [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 4679 - 4689

40
[ 635319-09-4 ]
(3R,4S)-4-(3-chlorophenylthiomethyl)-3-hydroxypyrrolidine hydrochloride [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 4679 - 4689

41
[ 635319-09-4 ]
[ 858930-19-5 ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 4679 - 4689

42
[ 635319-09-4 ]
(3R,4S)-4-(3-chlorophenylthiomethyl)-1-[(9-deazaadenin-9-yl)methyl]-3-hydroxypyrrolidine [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 4679 - 4689

43
[ 635319-09-4 ]
(3R,4S)-4-cyclohexylthiomethyl-3-hydroxypyrrolidine hydrochloride [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 4679 - 4689

44
[ 635319-09-4 ]
(3R,4S)-4-cyclohexylthiomethyl-1-[(9-deazaadenin-9-yl)methyl]-3-hydroxypyrrolidine [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 4679 - 4689

45
[ 635319-09-4 ]
[ 666831-19-2 ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 4679 - 4689

46
[ 635319-09-4 ]
[ 666831-18-1 ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 4679 - 4689

47
[ 635319-09-4 ]
[ 666831-17-0 ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 4679 - 4689

48
[ 635319-09-4 ]
acetic acid 1-(5-benzyloxymethyl-4-chloro-5H-pyrrolo[3,2-d]pyrimidin-7-ylmethyl)-4-methylsulfanylmethyl-pyrrolidin-3-yl ester [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 4679 - 4689

49
[ 635319-09-4 ]
(3R,4S)-1-[(6-tert-butoxy-7-benzyloxymethyl-9-deazapurin-9-yl)methyl]-3-acetoxy-4-(methylthiomethyl)pyrrolidine [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 4679 - 4689

50
[ 635319-09-4 ]
[ 666831-27-2 ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 4679 - 4689

51
[ 635319-09-4 ]
(3R,4S)-1-[8-aza-9-deaza-8-(tetrahydropyran-2-yl)adenin-9-yl]methyl-3-hydroxy-4-benzylthiomethylpyrrolidine [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 4679 - 4689

52
[ 635319-09-4 ]
[ 666831-22-7 ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 4679 - 4689

53
[ 635319-09-4 ]
acetic acid 1-(5-benzyloxymethyl-4-chloro-5H-pyrrolo[3,2-d]pyrimidin-7-ylmethyl)-4-benzylsulfanylmethyl-pyrrolidin-3-yl ester [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 4679 - 4689

54
[ 635319-09-4 ]
[ 666831-20-5 ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 4679 - 4689

55
[ 635319-09-4 ]
[ 666831-21-6 ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 4679 - 4689

56
[ 635319-09-4 ]
(3R,4S)-1-[(6-tert-butoxy-7-benzyloxymethyl-9-deazapurin-9-yl)methyl]-3-acetoxy-4-(benzylthiomethyl)pyrrolidine [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 4679 - 4689

57
[ 635319-09-4 ]
(3R,4S)-1-[(8-aza-9-deazaadenin-9-yl)methyl]-4-benzylthiomethyl-3-hydroxypyrrolidine dihydrochloride [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 4679 - 4689

58
[ 635319-09-4 ]
(3R,4S)-4-benzylthiomethyl-1-[(9-deazaadenin-9-yl)methyl]-3-hydroxypyrrolidine dihydrochloride [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 4679 - 4689

59
[ 635319-09-4 ]
(3R,4S)-4-benzylthiomethyl-3-hydroxypyrrolidine hydrochloride [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 4679 - 4689

60
[ 635319-09-4 ]
(3R,4R)-1-[(9-deazaadenin-9-yl)methyl]-3-hydroxy-4-(4-chlorophenylthiomethyl)pyrrolidine [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 4679 - 4689

61
[ 635319-09-4 ]
(3R,4R)-1-[(9-deazaadenin-9-yl)methyl]-3-hydroxy-4-(benzylthiomethyl)pyrrolidine [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 4679 - 4689

62
[ 635319-09-4 ]
(3R,4S)-4-(4-chlorophenylthiomethyl)-3-hydroxypyrrolidine hydrochloride [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 4679 - 4689

63
[ 635319-09-4 ]
(3R,4R)-3-acetoxy-4-acetoxymethylpyrrolidine hydrochloride [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2004,vol. 126,p. 5690 - 5698

64
[ 635319-09-4 ]
[ 705060-14-6 ]

Reference： [1]Journal of the American Chemical Society,2004,vol. 126,p. 5690 - 5698

65
[ 635319-09-4 ]
[ 705060-19-1 ]

Reference： [1]Journal of the American Chemical Society,2004,vol. 126,p. 5690 - 5698

66
[ 635319-09-4 ]
[ 705060-10-2 ]

Reference： [1]Journal of the American Chemical Society,2004,vol. 126,p. 5690 - 5698

67
[ 635319-09-4 ]
Phosphoric acid mono-[(3R,4R)-1-(3-carbamoyl-benzyl)-4-hydroxy-pyrrolidin-3-ylmethyl] ester [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2004,vol. 126,p. 5690 - 5698

68
[ 635319-09-4 ]
[(2R,3S,4R,5R)-5-(6-Amino-purin-9-yl)-3,4-dihydroxy-tetrahydro-furan-2-ylmethoxy]-hydroxy-phosphorylmethyl}-phosphonic acid mono-[(3R,4R)-1-(3-carbamoyl-benzyl)-4-hydroxy-pyrrolidin-3-ylmethyl] ester [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2004,vol. 126,p. 5690 - 5698

69
[ 635319-09-4 ]
[(3aR,4R,6R,6aR)-6-(6-Amino-purin-9-yl)-2,2-dimethyl-tetrahydro-furo[3,4-d][1,3]dioxol-4-ylmethoxy]-hydroxy-phosphorylmethyl}-phosphonic acid mono-[(3R,4R)-1-(3-carbamoyl-benzyl)-4-hydroxy-pyrrolidin-3-ylmethyl] ester; compound with ammonia [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2004,vol. 126,p. 5690 - 5698

70
[ 635319-09-4 ]
(3R,4R)-1-[(9-deazahypoxanthin-9-yl)methyl]-3-hydroxy-4-hydroxymethylpyrrolidine [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2003,vol. 46,p. 5271 - 5276

71
[ 635319-09-4 ]
(3R,4R)-1-[9-deazaguanin-9-yl]methyl}-3-hydroxy-4-hydroxymethylpyrrolidine [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2003,vol. 46,p. 5271 - 5276

72
[ 635319-09-4 ]
[ 635319-17-4 ]

Reference： [1]Journal of Medicinal Chemistry,2003,vol. 46,p. 5271 - 5276

73
[ 635319-09-4 ]
(3R,4R)-3-benzyloxy-4-benzyloxymethylpyrrolidine hydrochloride [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2003,vol. 46,p. 5271 - 5276

74
[ 635319-09-4 ]
(3R,4R)-1-[(8-aza-9-deazahypoxanthin-9-yl)methyl]-3-hydroxy-4-hydroxymethylpyrrolidine hydrochloride [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2003,vol. 46,p. 5271 - 5276

75
[ 635319-09-4 ]
[ 666830-86-0 ]

Reference： [1]Journal of Medicinal Chemistry,2003,vol. 46,p. 5271 - 5276

76
[ 635319-09-4 ]
[ 635319-15-2 ]

Reference： [1]Journal of Medicinal Chemistry,2003,vol. 46,p. 5271 - 5276

77
[ 635319-09-4 ]
[ 635319-16-3 ]

Reference： [1]Journal of Medicinal Chemistry,2003,vol. 46,p. 5271 - 5276

78
[ 6553-96-4 ]
[ 635319-09-4 ]
[ 666831-07-8 ]

Yield	Reaction Conditions	Operation in experiment
	In pyridine; at 20 - 60℃; for 17h;	2,4, 6-Triisopropylbenzenesulfonyl chloride (3.0 g) was added to a solution of 1 (1.0 g) in pyridine (20 mL) and the solution was stirred for 16 h, then was warmed to [60 C] for 1 h. Chloroform was added and the solution was washed with water, 2M aq HCI, and aq [NAHCO3.] Normal processing and chromatography gave 1.125 g of 34 as a colourless glass. A solution of 0.45 g of this material in DMF (5 mL) was treated with sodium thiomethoxide (0.2 g) and the mixture was stirred for 0.5 h. Toluene was added and the reaction was processed normally to give 0.115 g of crude material. A solution of this material in dichloromethane (5 mL) was treated with 4M HCI in dioxane (3 mL). After 1 h the solution was concentrated to dryness. The solid residue of 35 was dissolved in methanol (3 mL) containing 7-N-benzyloxymethyl- [9-DEAZA-6-O-METHYLHYPOXANTHINE-9-CARBALDEHYDE] (0.18 g), and sodium cyanoborohydride (0.088 g) was added. The mixture was stirred for 3 d. Chloroform was added and the mixture was processed normally. Chromatography then afforded 36 (0.178 [G).] This material in cHCI (10 mL) was heated under reflux for 1 h, then the solution was concentrated to dryness. The residue was treated with methanol/25 % aq [NH3] (1: 1) for 1 h and then concentrated to dryness. Chromatography afforded a solid material. This was dissolved in aq HCI and concentrated. Trituration of the residue with ethanol gave 37. [HC1] (0.048 g) as a hygroscopic white solid. 13C NMR [(D2O] at [85 C)] 8 154.6 (C), 144.5 (CH), 140.6 (C), 132.6 (CH), 118.6, 104.6 (C), 73.3 (CH), 59.3, 56.3, 48.0 [(CH2),] 45.7 (CH), 34.7 [(CH2),] 15.2 [(CH3).]

Reference： [1]Patent: WO2004/18496,2004,A1 .Location in patent: Page 39-40

79
(3S,4R)-1-tert-butyl 3-ethyl 4-hydroxypyrrolidine-1,3-dicarboxylate [ No CAS ]
[ 635319-09-4 ]

Yield	Reaction Conditions	Operation in experiment
90%	With methanol; lithium borohydride; In diethyl ether; for 0.5h;Heating / reflux;	Lithium borohydride (228 mg, 10.47 MMOL) was added to a solution of (3S, 4R)-4-HYDROXYPYRROLIDINE-1-N-3-DICARBOXYLIC acid-1-tert-butyl ester-3-ethyl ester from example 14 (12,1. 81 g, 6.98 MMOL) in anhydrous ET20 (27 mL) and methanol (0.49 mL, 12.22 MMOL) and the mixture heated under reflux with stirring for 30 mins (using the general method of K. Soai and A. Ookawa, J. Org. CHEM., 1986,51, 4000). After cooling, methanol (10 mL) was added and the solvent evaporated. The residue was dissolved in ethyl acetate and washed with sat NAHCO3, dried and evaporated to a colourless gum (1.48 g). It was chromatographed (eluant ethyl acetate-methanol 19: 1 v/v) to afford (3R, 4R)-3-HYDROXY4-HYDROXYMETHYLPYRROLIDIN-1-N-CARBOXYLIC acid tert-butyl ester (14) as a colourless gum (1.36 g, 90%). THE H AND 13C NMR were in agreement with that reported by G. B. Evans, R. H. Furneaux, A. Lewandocwicz, V. L. Schramm and P. C. Tyler, J. Med. CHEM., 2003,46, 5271. D +15. 5 (c 1.09, MEOH). A sample prepared as in G. B. Evans, R. H. Furneaux, A. Lewandocwicz, V. L. Schramm and P. C. Tyler, J. Med. CHEM., 2003,46, 5271, ultimately derived from D-xylose, had an [a] 21 +16 (c 0.795, MEOH).

Reference： [1]Patent: WO2005/33076,2005,A1 .Location in patent: Page/Page column 15; 29

80
[ 635319-09-4 ]
[ 848416-47-7 ]

Yield	Reaction Conditions	Operation in experiment
57%		Methanesulfonyl chloride(0.45 mL, 5.7 mmol) was added dropwise to a stirred solutionof <strong>[635319-09-4]tert-butyl 3-hydroxy-4-(hydroxymethyl)pyrrolidine-1-carboxylate</strong>(1) (1.13 g, 5.2 mmol) and 2,6-dimethylpyridine (1.2 mL,10.3 mmol) in acetone (20 mL) and the mixture left to stir for24 h. The resulting suspension was filtered to remove salt, andthen lithium bromide (2.25 g, 25.9 mmol) was added to thefiltrate and the mixture refluxed for 3 h, at which time thereaction was deemed complete. The crude reaction mixture wasabsorbed onto silica gel (5 g) and concentrated in vacuo and theresulting residue purified by chromatography (20% ? 40% ?100% EA/PE solvent) to afford title compound 2 (832 mg,57%) as a syrup: 1H NMR (500 MHz, CDCl3) delta 4.06 (brs,1H), 3.67 (brs, 2H), 3.47-3.36 (m, 2H), 3.28-3.18 (m, 2H),2.50 (brs, 1H), 1.46 (s, 9H); 13C NMR (125 MHz, CDCl3) delta154.6, 79.9, (73.3, 72.5), (52.6, 52.3), (48.8, 48.3), (48.2, 47.6),32.6, 28.5; HRMS (ESI) m/z calcd for C10H18NO3BrNa+302.0368, observed 302.0364.
	With carbon tetrabromide; triphenylphosphine; In dichloromethane; N,N-dimethyl acetamide; at 0 - 20℃; for 13h;	<Reference Example 16> Synthesis of (3R,4S)-3-cyclopropylaminomethyl-4-fluoropyrrolidine (Process IV) Step 1: (3R,4R)-(1-tert-Butoxycarbonyl-4-hydroxypyrrolidin-3-yl)methanol (3.64 g) and triphenylphosphine (4.41 g) were dissolved in N,N-dimethylacetamide (84 mL). While the solution was chilled in an ice water bath, carbon tetrabromide (5.57 g) in dichloromethane (16 mL) was added dropwise. The mixture was stirred at room temperature for 13 hours, followed by addition of methanol (8 mL) and concentration under reduced pressure. The resulting residue was dissolved in ethyl acetate (300 mL), washed sequentially with water (100 mL) and saturated brine (100 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (eluant: ethyl acetate: hexane = 2:1) to give (3S,4R)-3-bromomethyl-1-tert-butoxycarbonyl-4-hydroxypyrrolidine as a milky white syrup (3.17 g).MS (EI+) : m/z=279 (M+). HRMS (EI+) Calcd for C10H18BrNO3 (M+) : 279.0470 Found: 279.0471.

Reference： [1]Biochemistry,2017,vol. 56,p. 5090 - 5098
[2]Patent: EP1666477,2006,A1 .Location in patent: Page/Page column 24

81
[ 635319-09-4 ]
[ 267421-93-2 ]

Yield	Reaction Conditions	Operation in experiment
	Product distribution / selectivity;	A sample of the (3R,4ft)-enantiomer (+)- 10, prepared during the present work, and ultimately derived from D-glucose via the sequence (+)-6 ? (+)-7 ? (+)-8 ? (+)-10, had [alpha]*1 + 16.9 (c 0.935, H2O). The 1H NMR spectrum of compound (-)-10 was in agreement with the literature data for (+)-10 (G. B. Evans, R.H. Furneaux, A. Lewandowicz, V.L. Schramm and P.C. Tyler, J. Med. Chem., 2003, 46, 5271-5276) and with the spectrum of the latter isomer made during the present work.

Reference： [1]Patent: WO2007/69923,2007,A1 .Location in patent: Page/Page column 23

82
C₁₂H₂₃NO₆ [ No CAS ]
[ 635319-09-4 ]

Yield	Reaction Conditions	Operation in experiment
81%		The product was dissolved in EtOH (500 ml), cooled in an ice bath and oxidised by the dropwise addition of NaIO4 (47 g, 0.22 mol) in water (500 ml). After recooling of the products in an ice-bath the product was reduced with NaBH4 (7.3 g, 0.19 mmol) added portion-wise. The mixture was warmed to room temperature, the solids were removed by filtration, the volatiles by evaporation and the residue was purified by chromatography (CHCI3-MeOH, 9 : 1). Compound (+)-7 was obtained as a light yellow syrup (17 g, 81%) which gave 1H and 13C NMR data in agreement with those of the sample made by method A and with literature data (G.B. Evans, R.H. Furneaux, A. Lewandowicz, V.L. Schramm and P.C. Tyler, J. Med. Chem. 2003, 46, 5271-5276). A sample of compound (+)-7 (50 mg), prepared in this way, in EtOAc was further purified by washing with water and then brine to give a colourless syrup (28 mg) after solvent evaporation, [?]^1 + 16.2 (c 0.795, MeOH).
	Product distribution / selectivity;	A sample of the (3R,4ft)-enantiomer (+)- 10, prepared during the present work, and ultimately derived from D-glucose via the sequence (+)-6 ? (+)-7 ? (+)-8 ? (+)-10, had [alpha]*1 + 16.9 (c 0.935, H2O). The 1H NMR spectrum of compound (-)-10 was in agreement with the literature data for (+)-10 (G. B. Evans, R.H. Furneaux, A. Lewandowicz, V.L. Schramm and P.C. Tyler, J. Med. Chem., 2003, 46, 5271-5276) and with the spectrum of the latter isomer made during the present work.

Reference： [1]Patent: WO2007/69923,2007,A1 .Location in patent: Page/Page column 19; 21
[2]Patent: WO2007/69923,2007,A1 .Location in patent: Page/Page column 23

83
[ 98-88-4 ]
[ 635319-09-4 ]
[ 1011300-20-1 ]

Yield	Reaction Conditions	Operation in experiment
41%		Example 12: (3/?.4SH-r(9-Deaza-adenin-9-v0methylM-ethyl-3-hvdroxypyrrolidine (20. R = m; Example 12.1: (3/?,4R)-fert-butyl 4-(benzoyloxymethyl)-3-hydroxypyrrolidine-1- carboxylate (13); A solution of alcohol 12 (4.1O g, 19 mmol) and dibutyltin oxide (5.17 g, 21 mmol) in toluene (60 ml_) is refluxed in a Dean-Stark apparatus for 1 h. The solution is cooled to 5 0C and benzoyl chloride (2.2 ml_, 19 mmol) is added drop wise while the temperature is kept below 10 C. The mixture is stirred at room temperature for 17 h then concentrated under reduced pressure. Flash chromatography of the residue (40% EtOAc in Petrol) affords the title compound 13 as a yellow oil (2.48 g, 41%). 13C-NMR (125 MHz, CDCI3): delta = 171.3, 166.6, 154.6, 133.2, 129.6, 128.5, 79.7, 72.1 , 71.4, 64.1 , 60.4, 52.7, 52.5, 46.9, 46.4, 45.7, 45.2 and 28.5 ppm.

Reference： [1]Journal of the American Chemical Society,2008,vol. 130,p. 2166 - 2167
[2]Journal of Medicinal Chemistry,2010,vol. 53,p. 6730 - 6746
[3]Patent: WO2011/8110,2011,A1 .Location in patent: Page/Page column 51

84
[ 13057-17-5 ]
[ 635319-09-4 ]
[ 742079-58-9 ]

Yield	Reaction Conditions	Operation in experiment
45%		The diol 29 was manipulated according to Scheme 4 to afford 42.'H NMR (D20) 4.30- 4.26 (m, 1 H), 3.52-3. 28 (m, 4H), 3.22 (s, 3H), 3.15-3. 00 (m, 2H), 2.48-2. 37 (m, 1H). H).'3C NMR (D20) 72.1, 71.6, 58.8, 52.0, 46.7, 45.7. HRMS (MH+) calc for C6H14NO2 : 132.1019. Found 132.1012. (i) TBDPSCI, DMF (ii) HO NBoc, - HO (3 steps) . (2 steps) HO MOMS Im,29 R = Me, 42 R = Bn, 43 Scheme 4 Preparative Example 1.12 (3R, 4R)-4- (BENZYLOXYMETHYL)-3-HYDROXY-PYRROLIDINE (43), Scheme 4. The diol 29 was manipulated according to Scheme 4 to afford 43.'H NMR (D2O, free base) 7.32-7. 15 (m, 5H), 4.36 (s, 2H), 3.92-3. 85 (m, 1H), 3.35 (dd, J = 9.8, 7.0 Hz, 1H), 3.24 (dd, J= 9.8, 7.8 Hz, 1H), 2.97 (dd, J= 11.8, 7.9 Hz, 1H), 2.75 (dd, J= 12. 4,5. 5 Hz, 1H), 2.57 (dd, J= 12.4, 3.4 Hz, 1 H), 2.36 (dd, J = 11. 8,5. 7 Hz, 1H), 2.15-2. 05 (m, 1H). 13C NMR (D20) 137.6, 129.0, 128.8, 128.6, 74.7, 73.1, 71.0, 53.2, 48.0, 47.6. HRMS (MH+) calc for C12H18NO2 : 208.1332. Found 208. 1329.

Reference： [1]Patent: WO2004/69856,2004,A1 .Location in patent: Page 25-26

85
[ 76-83-5 ]
[ 635319-09-4 ]
C₂₉H₃₃NO₄ [ No CAS ]

Reference： [1]Carbohydrate Research,2010,vol. 345,p. 1831 - 1841

86
[ 635319-09-4 ]
[ 1261241-84-2 ]

Reference： [1]Patent: WO2011/8110,2011,A1

87
[ 635319-09-4 ]
[ 1242166-97-7 ]

Reference： [1]Patent: WO2011/8110,2011,A1

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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

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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
H304	May be fatal if swallowed and enters airways
H305	May be harmful if swallowed and enters airways
H310	Fatal in contact with skin
H311	Toxic in contact with skin
H312	Harmful in contact with skin
H313	May be harmful in contact with skin
H314	Causes severe skin burns and eye damage
H315	Causes skin irritation
H316	Causes mild skin irritation
H317	May cause an allergic skin reaction
H318	Causes serious eye damage
H319	Causes serious eye irritation
H320	Causes eye irritation
H330	Fatal if inhaled
H331	Toxic if inhaled
H332	Harmful if inhaled
H333	May be harmful if inhaled
H334	May cause allergy or asthma symptoms or breathing difficulties if inhaled
H335	May cause respiratory irritation
H336	May cause drowsiness or dizziness
H340	May cause genetic defects
H341	Suspected of causing genetic defects
H350	May cause cancer
H351	Suspected of causing cancer
H360	May damage fertility or the unborn child
H361	Suspected of damaging fertility or the unborn child
H361d	Suspected of damaging the unborn child
H362	May cause harm to breast-fed children
H370	Causes damage to organs
H371	May cause damage to organs
H372	Causes damage to organs through prolonged or repeated exposure
H373	May cause damage to organs through prolonged or repeated exposure
Environmental hazards
Code	Phrase
H400	Very toxic to aquatic life
H401	Toxic to aquatic life
H402	Harmful to aquatic life
H410	Very toxic to aquatic life with long-lasting effects
H411	Toxic to aquatic life with long-lasting effects
H412	Harmful to aquatic life with long-lasting effects
H413	May cause long-lasting harmful effects to aquatic life
H420	Harms public health and the environment by destroying ozone in the upper atmosphere

[ CAS No. 635319-09-4 ] {[proInfo.proName]}

Quality Control of [ 635319-09-4 ]

Related Doc. of [ 635319-09-4 ]

Product Details of [ 635319-09-4 ]

Safety of [ 635319-09-4 ]

Application In Synthesis of [ 635319-09-4 ]

[ 635319-09-4 ] Synthesis Path-Upstream 1~8

[ 635319-09-4 ] Synthesis Path-Downstream 1~87

Related Functional Groups of [ 635319-09-4 ]

Alcohols

Amides

Related Parent Nucleus of [ 635319-09-4 ]

Pyrrolidines

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Related Functional Groups of
[ 635319-09-4 ]

Related Parent Nucleus of
[ 635319-09-4 ]