Sodium Carbonate → 4-[4-(4-(Thiophen-2-yl)phenoxy)phenylsulfonylmethyl]-tetrahydropyran-4-carboxylic acid

HRID 1584401Notes

Reaction equation

HRID 1584401 reaction equation
Br[C:2]1[CH:27]=[CH:26][C:5]([O:6][C:7]2[CH:12]=[CH:11][C:10]([S:13]([CH2:16][C:17]3([C:23]([OH:25])=[O:24])[CH2:22][CH2:21][O:20][CH2:19][CH2:18]3)(=[O:15])=[O:14])=[CH:9][CH:8]=2)=[CH:4][CH:3]=1.[S:28]1[CH:32]=[CH:31][CH:30]=[C:29]1B(O)O.C(=O)([O-])[O-].[Na+].[Na+]>CN(C)C=O.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Pd]>[S:28]1[CH:32]=[CH:31][CH:30]=[C:29]1[C:2]1[CH:27]=[CH:26][C:5]([O:6][C:7]2[CH:8]=[CH:9][C:10]([S:13]([CH2:16][C:17]3([C:23]([OH:25])=[O:24])[CH2:18][CH2:19][O:20][CH2:21][CH2:22]3)(=[O:14])=[O:15])=[CH:11][CH:12]=2)=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 27339602-Thiopheneboronic acidHCID 212242044-[4-(4-Bromophenoxy)phenylsulfonylmethyl]-tetrahydropyran-4-carboxylic acid

Product 1

HCID 212241144-[4-(4-(Thiophen-2-yl)phenoxy)phenylsulfonylmethyl]-tetrahydropyran-4-carboxylic acidYield 94%

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 6228DimethylformamideSolvent

Procedure

To a solution of 4-[4-(4-bromophenoxy)phenylsulfonylmethyl]-tetrahydropyran-4-carboxylic acid (1.10 g, 2.42 mmol) of in N,N-dimethylformamide (15 mL) was added tetrakis(triphenylphosphine)palladium(O) (108 mg), 2-thiophene boronic acid (857 mg, 6.70 mmol), followed by 2M aqueous sodium carbonate (2.7 mL, 5.4 mmol). The reaction was heated to reflux for 10 hours, cooled to room temperature, and the mixture partitioned between methylene chloride (100 mL) and 1N aqueous hydrochloric acid (20 mL). The aqueous layer was back extracted with methylene chloride (100 mL), and the combined organic layers dried (MgSO4), the residue chromatographed over 100 g of silica gel (eluted with methylene chloride to 10% methanol/methylene chloride), and the resulting foam crystallized from the minimum amount of methylene chloride/hexanes to afford 4-[4-(4-(thiophen-2-yl)phenoxy)phenylsulfonylmethyl]-tetrahydropyran-4-carboxylic acid (1.04 g, 94%). mp 181.2-193.3° C.; IR (KBr) 3432 (br), 1718.9 cm-1 ; 1H NMR (DMSO-d6) δ 1.67 (ddd, J=13.8, 9.4, 4.0 Hz, 2H), 1.95 (dm, J=13.8 Hz, 2H), 3.47 (mc, 2H), 3.67 (mc, 2H), 3.68 (s, 2H), 7.14 (dd, J=4.9, 3.6 Hz, 1H), 7.20 (d, J=8.8 Hz, 2H), 7.22 (d, J=8.9 Hz, 2H), 7.50 (dd, J=3.6, 1.2 Hz, 1H), 7.54 (dd, J=4.9, 1.2 Hz, 1H), 7.74 (d, J=8.8 Hz, 2H), 7.87 (d, J=8.8 Hz, 2H), 12.80 (s, 1H); 13CNMR (DMSO-d6) δ 32.92 (t), 42.25 (s), 61.73 (t), 63.26 (t), 117.82 (d), 123.75 (d), 125.66 (d), 127.39 (d), 128.50 (d), 130.08 (d), 130.74 (s), 134.90 (s), 142.42 (s), 154.13 (s), 161.33 (s), 174.39 (s); FABHRMS Calcd. for C23H24S2O6 (M+ +H): 459.0936. Found: 459.0936. Anal. Calcd. for C23H23S2O6 : C, 60.24; H, 4.83. Found: C, 60.57; H, 4.90.

Workup

  1. temperatureThe reaction was heated
  2. temperatureto reflux for 10 hours
  3. customthe mixture partitioned between methylene chloride (100 mL) and 1N aqueous hydrochloric acid (20 mL)
  4. extractionThe aqueous layer was back extracted with methylene chloride (100 mL)
  5. dry with materialthe combined organic layers dried (MgSO4)
  6. customthe residue chromatographed over 100 g of silica gel (eluted with methylene chloride to 10% methanol/methylene chloride)
  7. customthe resulting foam crystallized from the minimum amount of methylene chloride/hexanes

Sources & evidence

ORD record
ord-ae04262f41b747e2acd0ba0448af2ffc
Source dataset
uspto-grants-1999_08
Patent number
US05932595

Reaction notes

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