Acetic Acid → 4-({(2S,5R)-1-(tert-butoxycarbonyl)-5-[(R)-{[tert-butyl(dimethyl)silyl]oxy}{6-[(2-phenylpropan-2-yl)amino]pyridin-3-yl}methyl]pyrrolidin-2-yl}methyl)benzoic acid

HRID 1911847Notes

Reaction equation

HRID 1911847 reaction equation
[Si:1]([O:8][C@H:9]([C:33]1[CH:34]=[N:35][C:36]([NH:39][C:40]([C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)([CH3:42])[CH3:41])=[CH:37][CH:38]=1)[C@H:10]1[CH2:14][CH2:13][C@@H:12]([CH2:15][C:16]2[CH:21]=[CH:20][C:19]([C:22]([O:24]C)=[O:23])=[CH:18][CH:17]=2)[N:11]1[C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[Li+].[OH-].C(O)(=O)C>O1CCOCC1.O.CCOC(C)=O>[C:29]([O:28][C:26]([N:11]1[C@@H:10]([C@H:9]([O:8][Si:1]([C:4]([CH3:6])([CH3:7])[CH3:5])([CH3:3])[CH3:2])[C:33]2[CH:34]=[N:35][C:36]([NH:39][C:40]([C:43]3[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=3)([CH3:41])[CH3:42])=[CH:37][CH:38]=2)[CH2:14][CH2:13][C@H:12]1[CH2:15][C:16]1[CH:17]=[CH:18][C:19]([C:22]([OH:24])=[O:23])=[CH:20][CH:21]=1)=[O:27])([CH3:30])([CH3:31])[CH3:32]

Participants

7

Reactant 3

HCID 176Acetic AcidHCID 3939Lithium HydroxideHCID 86670464tert-butyl (2R,5S)-2-[(R)-{[tert-butyl(dimethyl)silyl]oxy}{6-[(2-phenylpropan-2-yl)amino]pyridin-3-yl}methyl]-5-[4-(methoxycarbonyl)benzyl]pyrrolidine-1-carboxylate

Product 1

HCID 706558174-({(2S,5R)-1-(tert-butoxycarbonyl)-5-[(R)-{[tert-butyl(dimethyl)silyl]oxy}{6-[(2-phenylpropan-2-yl)amino]pyridin-3-yl}methyl]pyrrolidin-2-yl}methyl)benzoic acidYield 96%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution of tert-butyl (2R,5S)-2-[(R)-{[tert-butyl(dimethyl)silyl]oxy}{6-[(2-phenylpropan-2-yl)amino]pyridin-3-yl}methyl]-5-[4-(methoxycarbonyl)benzyl]pyrrolidine-1-carboxylate (0.340 g, 0.504 mmol) in dioxane (8 mL) and water (2 mL) was added 1M LiOH (1.51 mL, 1.51 mmol). The reaction was stirred vigorously at room temperature for 18 hours and then quenched with acetic acid (0.116 mL, 2.018 mmol). The reaction was diluted with EtOAc (125 mL) and washed with water (20 mL) and brine (20 mL). The organic extracts were dried over Na2SO4, filtered, and concentrated. The residue was taken up in CH2Cl2/heptanes and concentrated in vacuo to afford 4-({(2S,5R)-1-(tert-butoxycarbonyl)-5-[(R)-{[tert-butyl(dimethyl)silyl]oxy}{6-[(2-phenylpropan-2-yl)amino]pyridin-3-yl}methyl]pyrrolidin-2-yl}methyl)benzoic acid (319 mg, 96%). LC-MS=660.4 (M+1)+. 1H NMR (600 MHz, CD3OD) δ 7.90 (d, J=7.2 Hz, 2H), 7.79 (bs, 1H), 7.37 (bs, 2H), 7.28 (m, 1H), 7.02-7.12 (m, 5H), 6.13 (m, 1H), 5.31 & 5.12 (2 singlets, 1H), 4.00 (m, 1H), 3.84 (bs, 1H), 2.76 & 2.49 (2 multiplets, 1H), 1.14-1.96 (m, 20H), 0.88 (s, 9H), 0.08 (s, 3H), −0.06 (s, 3H).

Workup

  1. washwashed with water (20 mL) and brine (20 mL)
  2. dry with materialThe organic extracts were dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-dbd5b7a57dde4b7196fb3fbf297450be
Source dataset
uspto-grants-2013_12
Patent number
US08604038B2

Reaction notes

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