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| 1520 |
| | | Cortes loses control of Tenochtitlan and has to escape in haste with his men during 'the Sorrowful Night' | |
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| 1521 |
| | | After a little more than a year Cortes recaptures Tenochtitlan and finally establishes Spanish control over Mexico | |
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| 1525 |
| | | The conquistadors, settling on land granted to them after the conquest, begin the long process of European emigration to America | |
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| 1530 |
| | | Francisco Pizarro sails from Panama to attempt the conquest of Peru | |
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| 1531 |
| | | The Aztec Virgin of Guadalupe appears to an Indian near Mexico City and tells him she is 'one of his kind' | |
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| 1542 |
| | | New Laws are passed in Spain, in an attempt to protect the Indians on the encomiendas of Spanish America | |
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| c. 1550 |
| | | Spanish galleons assemble each year at Portobelo to deliver European goods and to ship home the metals of Latin America | |
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| c. 1570 |
| | | Privateers frequent the Spanish main to plunder the richly laden caravels on their way home to Europe | |
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| 1698 |
| | | Scotland makes a disastrous attempt to establish a colony in Darien, on the isthmus of Panama | |
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| 1789 |
| | | Alexander Mackenzie explores by canoe from central Canada through the Great Slave Lake to the Arctic Ocean | |
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