Potassium Phosphate, Tribasic → Methyl 2-((S)-6-((R)-4-(2,6-dimethyl-4-(methylcarbamoyl)phenyl)-7-fluoro-2,3-dihydro-1H-inden-1-yloxy)-2,3-dihydrobenzofuran-3-yl)acetate

HRID 237520Notes

Reaction equation

HRID 237520 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5](B2OC(C)(C)C(C)(C)O2)=[C:6]2[C:10]=1[C@H:9]([O:11][C:12]1[CH:25]=[CH:24][C:15]3[C@H:16]([CH2:19][C:20]([O:22][CH3:23])=[O:21])[CH2:17][O:18][C:14]=3[CH:13]=1)[CH2:8][CH2:7]2.I[C:36]1[C:45]([CH3:46])=[CH:44][C:39]([C:40]([NH:42][CH3:43])=[O:41])=[CH:38][C:37]=1[CH3:47].[O-]P([O-])([O-])=O.[K+].[K+].[K+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1>C1(C)C=CC=CC=1>[CH3:47][C:37]1[CH:38]=[C:39]([C:40](=[O:41])[NH:42][CH3:43])[CH:44]=[C:45]([CH3:46])[C:36]=1[C:5]1[CH:4]=[CH:3][C:2]([F:1])=[C:10]2[C:6]=1[CH2:7][CH2:8][C@H:9]2[O:11][C:12]1[CH:25]=[CH:24][C:15]2[C@H:16]([CH2:19][C:20]([O:22][CH3:23])=[O:21])[CH2:17][O:18][C:14]=2[CH:13]=1

Participants

6

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 86697106{(S)-6-[(R)-7-fluoro-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-indan-1-yloxy]-2,3-dihydro-benzofuran-3-yl}-acetic acid methyl esterHCID 866971824-iodo-N,3,5-trimethylbenzamide

Product 1

HCID 86697181Methyl 2-((S)-6-((R)-4-(2,6-dimethyl-4-(methylcarbamoyl)phenyl)-7-fluoro-2,3-dihydro-1H-inden-1-yloxy)-2,3-dihydrobenzofuran-3-yl)acetate

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
120 °C

Procedure

In a microwave vial, methyl 2-((S)-6-((R)-7-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1H-inden-1-yloxy)-2,3-dihydrobenzofuran-3-yl)acetate (75 mg), 4-iodo-N,3,5-trimethylbenzamide (93 mg), K3PO4 (102 mg) and dicyclohexyl(2′,6′-dimethoxybiphenyl-2-yl)phosphine (S-Phos) (7 mg) are suspended in toluene (1.8 mL) and water (0.2 mL) and purged for 10 minutes with argon. Palladium-(II)-acetate (4 mg) is added, the vial is sealed and the mixture is stirred at 120° C. for 5 hours. After cooling to ambient temperature the mixture is partitioned between ethyl acetate and water. The organic phase is dried (MgSO4) and concentrated. The residue is chromatographed on silica gel (cyclohexane/ethyl acetate 100:0→80:20) to give the title compound. Yield: 16 mg; LC (method 25): tR=1.32 min; Mass spectrum (ESI+): m/z=504 [M+H]+.

Workup

  1. customwater (0.2 mL) and purged for 10 minutes with argon
  2. additionPalladium-(II)-acetate (4 mg) is added
  3. customthe vial is sealed
  4. temperatureAfter cooling to ambient temperature the mixture
  5. customis partitioned between ethyl acetate and water
  6. dry with materialThe organic phase is dried (MgSO4)
  7. concentrationconcentrated
  8. customThe residue is chromatographed on silica gel (cyclohexane/ethyl acetate 100:0→80:20)

Sources & evidence

ORD record
ord-5d16a52398ea40e19aec555ce5a203e1
Source dataset
uspto-grants-2014_02
Patent number
US08642585B2

Reaction notes

Loading…