[CH3:1][O:2][C:3]([C:5]1(C(O)=O)[C:7]2([CH2:9][CH2:8]2)[CH2:6]1)=[O:4].C1C=CC(P([N:27]=[N+]=[N-])(C2C=CC=CC=2)=O)=CC=1.CCN(CC)CC.[ClH:37].O1CCOCC1>CC(O)(C)C>[ClH:37].[CH3:1][O:2][C:3]([C:5]1([NH2:27])[C:7]2([CH2:9][CH2:8]2)[CH2:6]1)=[O:4]
To a mixture of spiro[2.2]pentane-1,1-dicarboxylic acid methyl ester (400 mg, 2.30 mmol) in 3 mL of anhydrous t-BuOH was added 700 mg (2.50 mmol) of DPPA and 278 mg (2.70 mmol) of Et3N. The mixture was heated at reflux for 21 h and then partitioned between H2O and ether. The ether phase was dried over magnesium sulfate, filtered and concentrated in vacuo to yield an oil. To this oil was added 3 mL of a 4 M HCl/dioxane solution. This acidic solution was stirred at rt for 2 h and then concentrated in vacuo. The residue was triturated with ether to give 82 mg (20%) of 1-amino-spiro[2.2]pentane-1-carboxylic acid methyl ester hydrochloride salt as a white solid. 1H NMR (300 MHz, CDCl3) δ 9.19 (br s, 3 H), 3.81 (s, 3 H), 2.16, (d, J=5.5 Hz, 1 H), 2.01 (d, J=5.5 Hz, 1 H), 1.49 (m, 1 H), 1.24, (m, 1 H), 1.12 (m, 2 H). LRMS of free amine: MS m/z 142 (M++1). Section 2 of Example 12 The following P1′ intermediates were prepared as described: 1. Preparation of Cyclopropylsulfonamide (Alternate Route):
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