Diethyl Ether → (R)-Methyl 2-hydroxy-3-(2-(methoxymethyl)-7-methyl-2H-indazol-5-yl)propanoate

HRID 501939Notes

Reaction equation

HRID 501939 reaction equation
[OH-].[Na+].[CH2:3](OCC)C.CN(N=O)C(N[N+]([O-])=O)=N.[OH:18][C@H:19]([CH2:23][C:24]1[CH:32]=[C:31]([CH3:33])[C:30]2[C:26](=[CH:27][N:28]([CH2:34][O:35][CH3:36])[N:29]=2)[CH:25]=1)[C:20]([OH:22])=[O:21]>ClCCl>[OH:18][C@H:19]([CH2:23][C:24]1[CH:32]=[C:31]([CH3:33])[C:30]2[C:26](=[CH:27][N:28]([CH2:34][O:35][CH3:36])[N:29]=2)[CH:25]=1)[C:20]([O:22][CH3:3])=[O:21]

Participants

6

Reactant 4

HCID 3283Diethyl EtherHCID 14798Sodium HydroxideHCID 57794592(R)-2-Hydroxy-3-(2-(methoxymethyl)-7-methyl-2H-indazol-5-yl)propanoic AcidHCID 135436526N-Methyl-N'-nitro-N-nitrosoguanidine

Product 1

HCID 57794630(R)-Methyl 2-hydroxy-3-(2-(methoxymethyl)-7-methyl-2H-indazol-5-yl)propanoate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a heterogeneous mixture of 5 M sodium hydroxide (20 mL) and diethyl ether (60 mL) in a fire-polished erlenmeyer flask at 0° C. was added N-methyl-N′-nitro-N-nitrosoguanidine (1.17 g, 7.95 mmol) in small portions with swirling (no stirbar). After addition was complete, the mixture was allowed to stand at 0° C. for 15 min with occasional swirling. The ethereal was transferred in portions to a suspension of (R)-2-hydroxy-3-(2-(methoxymethyl)-7-methyl-2H-indazol-5-yl)propanoic acid (1.40 g, 5.30 mmol) in dichloromethane (20 mL) until the solid had all dissolved and a yellow color persisted. The reaction was allowed to rest at room temperature for ca. 5 min. before bubbling nitrogen through the solution to remove unreacted diazomethane. The reaction was concentrated and purified by column chromatography (50% to 75% ethyl acetate/hexanes) to give 1.47 g (100%) as a colorless oil. 1H-NMR (CDCl3, 500 MHz) δ 1.60 (bs, 1H), 2.58 (s, 3H), 2.95 (dd, J=13.9, 7.0, 1H), 3.14 (dd, J=13.9, 4.0, 1H), 3.36 (s, 3H), 3.76 (s, 3H), 4.46 (bm, 1H), 5.65 (s, 2H), 6.90 (s, 1H), 7.31 (s, 1H), 7.99 (s, 1H). Mass spec.: 279.11 (MH)+.

Workup

  1. additionAfter addition
  2. dissolutionall dissolved
  3. waitto rest at room temperature for ca. 5 min.
  4. custombefore bubbling nitrogen through the solution
  5. customto remove unreacted diazomethane
  6. concentrationThe reaction was concentrated
  7. custompurified by column chromatography (50% to 75% ethyl acetate/hexanes)
  8. customto give 1.47 g (100%) as a colorless oil

Sources & evidence

ORD record
ord-d1dfbe6cb5dc41f6825c3520a8e5e5ed
Source dataset
uspto-grants-2010_08
Patent number
US07772244B2

Reaction notes

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