(3R)-pyrrolidin-3-ol hydrochloride → HCID 24984105, compound

HRID 1724073Notes

Reaction equation

HRID 1724073 reaction equation
[O:1]=[C:2]1[N:6]([CH2:7][C:8]2[CH:13]=[CH:12][C:11]([C:14]3[CH:19]=[CH:18][C:17]([CH:20]=O)=[CH:16][CH:15]=3)=[CH:10][CH:9]=2)[CH2:5][C:4]2([CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]2)[O:3]1.Cl.[NH:28]1[CH2:32][CH2:31][C@@H:30]([OH:33])[CH2:29]1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>ClCCCl>[OH:33][CH:30]1[CH2:31][CH2:32][N:28]([CH2:20][C:17]2[CH:16]=[CH:15][C:14]([C:11]3[CH:12]=[CH:13][C:8]([CH2:7][N:6]4[CH2:5][C:4]5([CH2:22][CH2:23][CH2:24][CH2:25][CH2:26]5)[O:3][C:2]4=[O:1])=[CH:9][CH:10]=3)=[CH:19][CH:18]=2)[CH2:29]1

Participants

5

Reactant 3

HCID 2759336(3R)-pyrrolidin-3-ol hydrochlorideHCID 5049666Sodium triacetoxyborohydrideHCID 24983951HCID 24983951, compound

Product 1

HCID 24984105HCID 24984105, compoundYield 56.5%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

4′-(2-Oxo-1-oxa-3-aza-spiro[4.5]dec-3-ylmethyl)-biphenyl-4-carbaldehyde (50 mg, 0.143 mmol) was mixed with (R)-(−)-3-pyrrolidinol hydrochloride (20 mg, 0.157 mmol) in DCE (2.5 mL). Na(OAc)3BH was added as a solid at room temperature and the reaction was stirred overnight. The reaction was quenched with saturated aqueous NaHCO3 solution. The aqueous phase was extracted with DCM (3×5 mL), the combined organic phases were washed with brine (5 mL), dried over sodium sulfate and concentrated. The crude residue was purified on silica gel eluting with DCM containing 0.5˜2% 2M ammonia in methanol to give the product as off-white solid (34 mg, 56.5%). 1H NMR (300 MHz, CDCl3): δ (ppm) 7.59 (dd, 4H), 7.38 (d, 2H), 7.29 (d, 2H), 4.42 (s, 2H), 4.37 (m, 1H), 3.69 (s, 2H), 3.13 (s, 2H), 2.87 (m, 1H), 2.67 (d, 1H), 2.58 (dd, 1H), 2.37 (m, 2H), 2.2 (m, 1H), 1.76 (m, 4H), 1.51 (m, 6H).

Workup

  1. customThe reaction was quenched with saturated aqueous NaHCO3 solution
  2. extractionThe aqueous phase was extracted with DCM (3×5 mL)
  3. washthe combined organic phases were washed with brine (5 mL)
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated
  6. customThe crude residue was purified on silica gel eluting with DCM containing 0.5˜2% 2M ammonia in methanol

Sources & evidence

ORD record
ord-72983d5cd13445018b5acff9adae7e22
Source dataset
uspto-grants-2009_02
Patent number
US07485722B2

Reaction notes

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