Lithium hydroxide, monohydrate → tert-butyl 5-chloro-1-((5R,7R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4'-piperidine]-1'-carboxylate

HRID 2190006Notes

Reaction equation

HRID 2190006 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:10]3([CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12][CH2:11]3)[CH2:9][N:8]([C:23]3[C:24]4[C@H:31]([CH3:32])[CH2:30][C@@H:29]([O:33]C(=O)C5C=CC([N+]([O-])=O)=CC=5)[C:25]=4[N:26]=[CH:27][N:28]=3)[C:5]2=[CH:6][CH:7]=1.O[Li].O>C1COCC1.O>[Cl:1][C:2]1[CH:3]=[C:4]2[C:10]3([CH2:11][CH2:12][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:14][CH2:15]3)[CH2:9][N:8]([C:23]3[C:24]4[C@H:31]([CH3:32])[CH2:30][C@@H:29]([OH:33])[C:25]=4[N:26]=[CH:27][N:28]=3)[C:5]2=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 68762968HCID 68762968, compound

Product 1

HCID 68759438tert-butyl 5-chloro-1-((5R,7R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4'-piperidine]-1'-carboxylateYield 36%

Reagents, catalysts & solvents 1

HCID 21881883Oxolane--water (1/1)Solvent

Conditions

Temperature
0 °C

Procedure

A solution of tert-butyl 5-chloro-1-((5R,7R)-5-methyl-7-(4-nitrobenzoyloxy)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-1′-carboxylate (0.020 g, 0.032 mmol) in THF:H2O (2:1, 0.3 mL) was cooled to about 0° C. and treated with LiOH—H2O (0.0027 g, 0.065 mmol). The reaction was stirred at about 0° C. for about 5 minutes, followed by about room temperature for 1.5 hours. The reaction was concentrated and diluted with saturated NaHCO3 and extracted with EtOAc. The combined extracts were washed with brine, dried over MgSO4, filtered and concentrated. Crude residue was purified by preparative HPLC to yield tert-butyl 5-chloro-1-((5R,7R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-1′-carboxylate (0.005 g, 36%). LCMS (APCI+) m/z 471, 473 [M+H]+; Rt=4.11 min.

Workup

  1. waitfollowed by about room temperature for 1.5 hours
  2. concentrationThe reaction was concentrated
  3. additiondiluted with saturated NaHCO3
  4. extractionextracted with EtOAc
  5. washThe combined extracts were washed with brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customCrude residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-58ab98c0a0fe4e8da405a010665f595b
Source dataset
uspto-grants-2012_12
Patent number
US08324221B2

Reaction notes

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