Water → 2-((1-(2-Adamantyloxycarbonyl)-4-phenylpiperidin-4-yl)methoxy)acetic acid

HRID 1752319Notes

Reaction equation

HRID 1752319 reaction equation
C[O:2][C:3](=[O:32])[CH2:4][O:5][CH2:6][C:7]1([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[CH2:12][CH2:11][N:10]([C:13]([O:15][CH:16]2[CH:23]3[CH2:24][CH:19]4[CH2:20][CH:21]([CH2:25][CH:17]2[CH2:18]4)[CH2:22]3)=[O:14])[CH2:9][CH2:8]1.O[Li].O.O.CC[NH+](CC)CC.CC[NH+](CC)CC.C([O-])([O-])=O>C1COCC1.CO.C(Cl)Cl>[CH:17]12[CH2:25][CH:21]3[CH2:20][CH:19]([CH2:24][CH:23]([CH2:22]3)[CH:16]1[O:15][C:13]([N:10]1[CH2:9][CH2:8][C:7]([CH2:6][O:5][CH2:4][C:3]([OH:32])=[O:2])([C:26]3[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=3)[CH2:12][CH2:11]1)=[O:14])[CH2:18]2

Participants

8

Reactant 4

HCID 962WaterHCID 168937Lithium hydroxide, monohydrateHCID 15264167Carbonic acid--N,N-diethylethanamine (1/2)HCID 581715042-Adamantyl 4-((2-methoxy-2-oxoethoxy)methyl)-4-phenylpiperidine-1-carboxylate

Product 1

HCID 581715092-((1-(2-Adamantyloxycarbonyl)-4-phenylpiperidin-4-yl)methoxy)acetic acidYield 4.4%

Reagents, catalysts & solvents 3

HCID 887MethanolSolvent2×HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 2-adamantyl 4-((2-methoxy-2-oxoethoxy)methyl)-4-phenylpiperidine-1-carboxylate (17.5 mg, 0.04 mmol) in THF (0.5 mL) and MeOH (1 mL) were added LiOH.H2O (8.3 mg, 0.2 mmol) and water (0.5 mL). The mixture was stirred at rt for 18 h and submitted directly to prep HPLC. The product from prep HPLC (8.3 mg) was stirred gently with MP-carbonate resin (75 mg), MeOH (2 mL) and CH2Cl2 (2 mL) for 22 h. The mixture was filtered and the resin beads collected were resuspended in 20:1 CH2Cl2/TFA (5 mL) overnight. The mixture was filtered and the filtrate was concentrated to leave crude material (2.5 mg). This material was purified by prep HPLC to afford the title compound (0.75 mg). LC-MS Method 1 tR=2.12 min, m/z=428.

Workup

  1. filtrationThe mixture was filtered
  2. customthe resin beads collected
  3. customwere resuspended in 20:1 CH2Cl2/TFA (5 mL) overnight
  4. filtrationThe mixture was filtered
  5. concentrationthe filtrate was concentrated
  6. customto leave crude material (2.5 mg)
  7. customThis material was purified by prep HPLC

Sources & evidence

ORD record
ord-2b81b67d7d4842b2868c135fcda94c1c
Source dataset
uspto-grants-2015_10
Patent number
US09163012B2

Reaction notes

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