Tetrabutylammonium Fluoride → 4-(4-((R)-(4'-chlorobiphenyl-2-yl)(hydroxy)methyl)piperidin-1-yl)-N-(4-((R)-4-morpholino-1-(phenylthio)butan-2-ylamino)-3-nitrophenylsulfonyl)benzamide

HRID 1476351Notes

Reaction equation

HRID 1476351 reaction equation
[Si]([O:8][C@@H:9]([C:55]1[CH:60]=[CH:59][CH:58]=[CH:57][C:56]=1[C:61]1[CH:66]=[CH:65][C:64]([Cl:67])=[CH:63][CH:62]=1)[CH:10]1[CH2:15][CH2:14][N:13]([C:16]2[CH:54]=[CH:53][C:19]([C:20]([NH:22][S:23]([C:26]3[CH:31]=[CH:30][C:29]([NH:32][C@H:33]([CH2:42][CH2:43][N:44]4[CH2:49][CH2:48][O:47][CH2:46][CH2:45]4)[CH2:34][S:35][C:36]4[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=4)=[C:28]([N+:50]([O-:52])=[O:51])[CH:27]=3)(=[O:25])=[O:24])=[O:21])=[CH:18][CH:17]=2)[CH2:12][CH2:11]1)(C(C)(C)C)(C)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>>[Cl:67][C:64]1[CH:65]=[CH:66][C:61]([C:56]2[CH:57]=[CH:58][CH:59]=[CH:60][C:55]=2[C@H:9]([OH:8])[CH:10]2[CH2:11][CH2:12][N:13]([C:16]3[CH:17]=[CH:18][C:19]([C:20]([NH:22][S:23]([C:26]4[CH:31]=[CH:30][C:29]([NH:32][C@H:33]([CH2:42][CH2:43][N:44]5[CH2:45][CH2:46][O:47][CH2:48][CH2:49]5)[CH2:34][S:35][C:36]5[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=5)=[C:28]([N+:50]([O-:52])=[O:51])[CH:27]=4)(=[O:25])=[O:24])=[O:21])=[CH:53][CH:54]=3)[CH2:14][CH2:15]2)=[CH:62][CH:63]=1

Participants

3

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 866618754-(4-((R)-(tert-butyldimethylsilyloxy)(4'-chlorobiphenyl-2-yl)methyl)piperidin-1-yl)-N-(4-((R)-4-morpholino-1-(phenylthio)butan-2-ylamino)-3-nitrophenylsulfonyl)benzamide2×

Product 1

HCID 667237894-(4-((R)-(4'-chlorobiphenyl-2-yl)(hydroxy)methyl)piperidin-1-yl)-N-(4-((R)-4-morpholino-1-(phenylthio)butan-2-ylamino)-3-nitrophenylsulfonyl)benzamideYield 79.4%

Procedure

4-(4-((R)-(tert-butyldimethylsilyloxy)(4′-chlorobiphenyl-2-yl)methyl)piperidin-1-yl)-N-(4-((R)-4-morpholino-1-(phenylthio)butan-2-ylamino)-3-nitrophenylsulfonyl)benzamide (INTERMEDIATE 75, 329.0 mg, 0.33 mmol) was charged in a 100 ml flask under nitrogen and treated with TBAF (10.0 ml, 1.0 M in THF, 10 mmol). The resulting solution was stirred at room temperature for 35 minutes whereupon the volatiles were removed under reduced pressure. The concentrate was diluted with DCM (100 ml) and washed with 1N aq. NaHSO4 (100 ml), and saturated aq. NaHCO3 (30 ml), then dried (Na2SO4), filtered, and evaporated under vacuum. The concentrate was purified by column chromatography (ISCO, 12 g silica gel column, eluting with 0→5% MeOH/DCM) followed by further purification by column chromatography (ISCO, 12 g silica gel column, eluting with 0→90% DCM/[10% of 2M NH3 in MeOH/90% DCM]) to provide the title product (228 mg, yield: 78%)

Workup

  1. customwere removed under reduced pressure
  2. additionThe concentrate was diluted with DCM (100 ml)
  3. washwashed with 1N aq. NaHSO4 (100 ml), and saturated aq. NaHCO3 (30 ml)
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. customevaporated under vacuum
  7. customThe concentrate was purified by column chromatography (ISCO, 12 g silica gel column, eluting with 0→5% MeOH/DCM)
  8. customfollowed by further purification by column chromatography (ISCO, 12 g silica gel column, eluting with 0→90% DCM/[10% of 2M NH3 in MeOH/90% DCM])

Sources & evidence

ORD record
ord-18914a074f464e19bef7bb6555ef0596
Source dataset
uspto-grants-2015_04
Patent number
US09018381B2

Reaction notes

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