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Chemical Structure| 131992-30-8

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Product Details of [ 131992-30-8 ]

CAS No. :131992-30-8
Formula : C7H12OS
M.W : 144.23
SMILES Code : COC=C1CCSCC1
MDL No. :MFCD27943574
InChI Key :GYDWKLRCVMKVBG-UHFFFAOYSA-N
Pubchem ID :20699606

Safety of [ 131992-30-8 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H302-H319-H372-H410
Precautionary Statements:P273-P301+P312+P330-P305+P351+P338-P314
Class:9
UN#:3082
Packing Group:

Application In Synthesis of [ 131992-30-8 ]

* 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 [ 131992-30-8 ]

[ 131992-30-8 ] Synthesis Path-Downstream   1~2

  • 1
  • [ 131992-30-8 ]
  • [ 23719-80-4 ]
  • [ 658-27-5 ]
  • 2-cyclopropyl-6-fluoro-1,2,2’,3’,5’,6’-hexahydrospiro[indole-3,4’-thiopyran] [ No CAS ]
  • 2-cyclopropyl-4-fluoro-1,2,2’,3’,5’,6’-hexahydrospiro[indole-3,4’-thiopyran] [ No CAS ]
YieldReaction ConditionsOperation in experiment
Similar to Liu et al., Tetrahedron 2010, 66,3,573-577 orWO10/151737, p.224. To a stirred solution of 1 eq. of hydrazine 1 (for 3a and 3b) or 11 (for 12a and 12b) or its corresponding hydrochloride salt and 1 eq. of carbonyl compound 2 or enol ether 10 in chloroform (ca 5.5 mL/mmol) at rt, 3.3 eq. of trifluoroacetic acid are added dropwise. The reaction mixture is heated to 50 C until TLC and/or LCMS indicate complete consumption of the starting material (4 h) and then cooled to room temperature. An aqueous solution of ammonia (25%) is carefully added to reach a pH of 10. The mixture is poured into water, the phases are separated and the aqueous phase extracted twice with dichloromethane. The combined organic layers are washed twice with water, dried with magnesium sulfate and the solvents removed in vacuo. The crude product mixture of regioisomers is taken to the next step without further purification. According to GP 1, 1 eq. of (4-bromo-3-chlorophenyl)hydrazine (MAYBRIDGE RF 01375, 3.21 g, 14.5 mmol) and 1 eq. of 4-(methoxymethylene)-3,4,5,6-tetrahydro-2H-thiopyran(2.09 g, 14.5 mmol, from step 1)were reacted with 3.3 eq. trifluoroacetic acid (3.7 mL, 48 mmol) in 80 mL chloroform for 4 h. The obtained crude product mixture (5.6 g) was taken to the next step without further purification. UPLC-MS (ESI+): [M + H]+ = 316/318/320 (Br/Cl isotope pattern). To a stirred and degassed solution of indolenine mixture 3a and 3b or 12a and 12b in THF (ca 3.5 mL/mmol), 1 eq. of boron trifluoride diethylether complex is added dropwise at 0C. After 5 min of stirring, 3.5 eq. of the corresponding Grignard reagent (commercial 0.5-1 M solution in THF or prepared from the respective alkyl bromide according to standard procedures) are added dropwise within approximately 1 h, keeping the temperature of the mixture at 5C. The mixture is further stirred at 0 C until TLC and/or LCMS indicate complete consumption of the starting material (5 min to 0.5 h). Then sat. aqueous ammonium chloridesolution is added and the mixture partitioned between ethyl acetate and water. The aqueous phase is extracted with ethyl acetate, the combined organic phases are washed with water, brine, dried with magnesium sulfate, concentrated in vacuo and purified via flash chromatography (SiO2-hexane/ethyl acetate) to give the desired 4,5-disubstituted or 4-substituted regioisomers. According to GP 2 the regioisomeric mixture of intermediate A.2 (3.0 g, 13.6 mmol), 3.5 eq. cyclopropylmagnesium bromide (96 mL of a 0.5 M solution in THF, 48 mmol) and 1 eq. (1.7 mL, 13.6 mmol) borontrifluoride etherate were reacted in 50 mL THF THF for 70 min to yield 526 mg (15%) of intermediate B.2 after flash chromatography (SiO2-hexane/ethylacetate) along with the 6-regioisomer. 1H-NMR (400MHz, DMSO-d6): Shift [ppm] = 0.18-0.24 (m, 1 H), 0.39 - 0.48 (m, 2H), 0.51 - 0.58 (m, 1 H), 0.89 - 0.97 (m, 1 H), 1.82 - 1.96 (m,2H), 2.29 - 2.42 (m, 2H), 2.56 - 2.62 (m, 2H), 2.81 - 2.87 (m, 2H), 2.95 (d, 1 H), 5.89 (s, 1 H),6.24 (dd, 1 H), 6.29 (d, 1 H), 6.89 - 6.94 (m, 1 H). UPLC-MS (ESl+): [M + H]+ = 264.
810 mg; 526 mg Intermediate A.1 Preparation of 4-fluoro-2',3',5',6'-tetrahydrospiro[indole-3,4'-thiopyran] and 6-fluoro-2',3',5',6'-tetrahydro[indole-3,4'-thiopyran] To a stirred solution of <strong>[658-27-5](3-fluorophenyl)hydrazine</strong> (CAS No. [658-27-5], 1 .83 g, 14.5 mmol) and 4-(methoxymethylene)-3,4,5,6-tetrahydro-2H-thiopyran (2.09 g, 14.5 mmol) in 80 mL chloroform at rt, trifluoroacetic acid (3.7 ml_, 48 mmol) was added dropwise. The reaction mixture was heated to 50C for 4 h and then cooled to room temperature. An aqueous solution of ammonia (25%) was carefully added to reach a pH of ~ 10. The mixture was poured into water, the phases were separated and the aqueous phase extracted twice with dichloromethane. The combined organic layers were washed twice with water, dried with magnesium sulfate and the solvents removed in vacuo. The crude product mixture (3.0 g) of regioisomers was taken to the next step without further purification. UPLC-MS (ESI+): [M + H]+= 222 Rt = 1.05/1.07 min. Intermediate B.1 Preparation of 2-cyclopropyl-4-fluoro-1,2,2',3',5',6'-hexahydrospiro[indole-3,4'-thiopyran] B.1 and 2-cyclopropyl-6-fluoro-1,2,2',3',5',6'-hexahydrospiro[indole-3,4'-thiopyran] B.2 To a stirred and degassed solution of indolenine mixture A.1 in 35 mL THF (3.0 g,13.6 mmol) boron trifluoride diethylether complex (1.7 mL, 13.6 mmol) was added dropwise at 0C. After 5 min of stirring cyclopropylmagnesium bromide (96 mL of a 0.5 M solution in THF, 48 mmol) was added dropwise within approximately 1 h, keeping the temperature of the mixture at 5C. The mixture was further stirred at 0C until TLC and/or LCMS indicated complete consumption of the starting material. Then sat. aqueous ammonium chloride solution was added and the mixture partitioned between ethyl acetate and water. The aqueous phase was extracted with ethyl acetate, the combined organic phases were washed with water and brine, dried with magnesium sulfate, concentrated in vacuo and purified via flash chromatography (SiO2-hexane/ethyl acetate) to give 526 mg (15%) of intermediate B.1 and 810 mg (22 %) of intermediate B.2. B.1 1H-NMR (400MHz, DMSO-d6): Shift [ppm] = 0.18 - 0.24 (m, 1 H), 0.39 - 0.48 (m, 2H), 0.51 - 0.58 (m, 1 H), 0.89 - 0.97 (m, 1 H), 1.82 - 1.96 (m, 2H), 2.29 - 2.42 (m, 2H), 2.56 - 2.62 (m, 2H), 2.76 - 2.90 (m, 2H), 2.95 (d, 1 H), 5.89 (s, 1 H), 6.24 (dd, 1 H), 6.29 (d, 1 H), 6.89 - 6.94 (m, 1 H). UPLC-MS (ESI+): [M + H]+= 264 Rt = 1.39 min. B.2 1H-NMR (400MHz, DMS0-d6): Shift [ppm] = 0.12 - 0.22 (m, 1 H), 0.32 - 0.46 (m, 2H), 0.47 - 0.57 (m, 1 H), 0.79 - 0.93 (m, 1 H), 1.79 - 2.03 (m, 2H), 2.08 - 2.20 (m, 1 H), 2.65 - 2.77 (m, 4H), 2.80 (d, 1 H), 5.91 (s, 1 H), 6.17 - 6.30 (m, 2H), 7.04 - 7.14 (m, 1 H). UPLC-MS (ESI+): [M + H]+= 264 Rt = 1.39 min.
  • 2
  • [ 131992-30-8 ]
  • [ 658-27-5 ]
  • 4-fluoro-2’,3’,5’,6’-tetrahydrospiro[indole-3,4’-thiopyran] [ No CAS ]
  • 6-fluoro-2’,3’,5’,6’-tetrahydrospiro[indole-3,4’-thiopyran] [ No CAS ]
YieldReaction ConditionsOperation in experiment
With trifluoroacetic acid; In chloroform; at 50℃; for 4h; To a stirred solution of <strong>[658-27-5](3-fluorophenyl)hydrazine</strong> (CAS No. [658-27-5], 1 .83 g, 14.5 mmol) and 4-(methoxymethylene)-3,4,5,6-tetrahydro-2H-thiopyran (2.09 g, 14.5 mmol) in 80 mL chloroform at rt, trifluoroacetic acid (3.7 ml_, 48 mmol) was added dropwise. The reaction mixture was heated to 50C for 4 h and then cooled to room temperature. An aqueous solution of ammonia (25%) was carefully added to reach a pH of ~ 10. The mixture was poured into water, the phases were separated and the aqueous phase extracted twice with dichloromethane. The combined organic layers were washed twice with water, dried with magnesium sulfate and the solvents removed in vacuo. The crude product mixture (3.0 g) of regioisomers was taken to the next step without further purification. UPLC-MS (ESI+): [M + H]+= 222 Rt = 1.05/1.07 min.
 

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