Sodium Carbonate Monohydrate → (S)-methyl 2-(1-(2,3-difluorobenzyl)-4-iodo-6-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-2-hydroxyacetate

HRID 1912619

반응식

HRID 1912619 반응식
[F:1][C:2]1[C:25]([F:26])=[CH:24][CH:23]=[CH:22][C:3]=1[CH2:4][N:5]1[C:9]2=[N:10][C:11]([CH3:21])=[C:12]([C:15](=[O:20])[C:16]([O:18][CH3:19])=[O:17])[C:13]([I:14])=[C:8]2[CH:7]=[CH:6]1.CB1N2CCC[C@@H]2C(C2C=CC=CC=2)(C2C=CC=CC=2)O1.CCO.C(=O)=O.C([O-])([O-])=O.[Na+].[Na+].O>C1(C)C=CC=CC=1.O.CCOC(C)=O.C1COCC1>[F:1][C:2]1[C:25]([F:26])=[CH:24][CH:23]=[CH:22][C:3]=1[CH2:4][N:5]1[C:9]2=[N:10][C:11]([CH3:21])=[C:12]([C@H:15]([OH:20])[C:16]([O:18][CH3:19])=[O:17])[C:13]([I:14])=[C:8]2[CH:7]=[CH:6]1

참가 물질

9

반응물 4

HCID 2735133Sodium Carbonate MonohydrateHCID 9838490(R)-2-Methyl-CBS-oxazaborolidineHCID 19604758Methanedione--ethanol (1/1)HCID 71209320methyl 2-(1-(2,3-difluorobenzyl)-4-iodo-6-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-2-oxoacetate

생성물 1

HCID 71209254(S)-methyl 2-(1-(2,3-difluorobenzyl)-4-iodo-6-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-2-hydroxyacetate수율 100%

시약·촉매·용매 4

HCID 962Water용매HCID 1140Toluene용매2회HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매

반응 조건

온도
0 °C

실험 절차

To a solution of methyl 2-(1-(2,3-difluorobenzyl)-4-iodo-6-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-2-oxoacetate (5.8 g, 12.33 mmol) in toluene (120 mL) was added (R)-1-methyl-3,3-diphenylhexahydropyrrolo[1,2-c][1,3,2]oxazaborole [(R)-CBS, 0.855 g, 3.08 mmol) (1M/toluene) under nitrogen atmosphere and the mixture was cooled to −35° C. (EtOH/dry ice); then cathecolborane (38.2 mL, 38.2 mmol) (1M/THF) was slowly added in ˜30 min. The mixture was kept at −35° C. 30 min and then allowed to warm to 0° C. in ˜2 h. 2M Na2CO3/water was added followed by EtOAc and the mixture was stirred for 5 min at ambient temperature. Water was added and the organic phase was washed with 1M NaOH/water (2×), dried (Na2SO4), concentrated, dried in vacuo to provide (S)-methyl 2-(1-(2,3-difluorobenzyl)-4-iodo-6-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-2-hydroxyacetate (6.84 g, 12.31 mmol, 100% yield) as a yellowish solid. Chiral HPLC showed ˜97:3 selectivity. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 2.62 (s, 3 H), 3.78 (s, 3 H), 5.49 (d, J=15.24 Hz, 1 H), 5.52 (d, J=15.24, 1 H), 5.92 (s, 1 H), 6.34 (d, J=3.52 Hz, 1 H), 6.81-6.90 (m, 1 H), 6.91-7.01 (m, 1 H), 7.02-7.12 (m, 1 H), 7.20 (d, J=3.52 Hz, 1 H); LCMS (m/z) ES+=473 (M+1).

후처리

  1. customwas kept at −35° C
  2. custom30 min
  3. washthe organic phase was washed with 1M NaOH/water (2×)
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated
  6. customdried in vacuo

출처 및 근거

ORD 기록
ord-78255c1520644c46ad7e608e314a2f2e
출처 데이터셋
uspto-grants-2013_12
특허 번호
US08609653B2

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